Obesity is associated with incident chronic kidney disease in individuals with normal renal function.

BACKGROUND/AIMS: Obesity has known to be a modifiable risk factor associated with worse outcomes in chronic kidney disease (CKD), but few studies have examined the impact of obesity on CKD incidence in the general population. The purpose of this study was to investigate the role of body mass index (BMI) and waist-to-hip ratio (WHR) as predictors of incident CKD and to evaluate the impact of weight reduction on CKD prevention. METHODS: A total of 2,711 participants from a community-based cohort with normal renal function were prospectively analyzed. Among participants with obesity, we analyzed the change in WHR to evaluate the association of obesity reduction with CKD development. RESULTS: During a mean follow-up of 11.03 ± 4.22 years, incident CKD occurred in 190 (7.0%) participants. In the fully adjusted multivariable Cox proportional hazard models, the risk of incident CKD increased with higher BMI (hazard ratio, 1.06; 95% confidence interval, 1.00-1.11; p = 0.033) and higher WHR (hazard ratio, 1.33; 95% confidence interval, 1.07-1.66; p = 0.009). In the Kaplan-Meier analysis, cumulative adverse renal events were significantly more common in the maintained obesity group than in the reduced obesity group (p = 0.001). CONCLUSION: Both higher BMI and WHR were associated with development of CKD, but the magnitude of the effect of WHR was higher than that of BMI. Moreover, reducing obesity would be beneficial for renal prognosis.

Systematic metabolomics study in the serum and urine of a mouse model of Fabry disease.

Background: Fabry disease (FD) is an X-linked lysosomal disorder caused by α-galactosidase A enzyme activity deficiency. Although glycosphingolipid analogs have been identified in the plasma or urine of patients with FD, there is a limited understanding of altered metabolomics profiles beyond the globotriaosylceramide accumulation in FD. Methods: Metabolomics study was performed for monitoring of biomarker and altered metabolism related with disease progression in serum and urine from male α-galactosidase A knockout mice and age-matched wild-type mice at 20 and 40 weeks. Profiling analysis for metabolites, including organic acids, amino acids, fatty acids, kynurenine pathway metabolites, and nucleosides in the serum and urine was performed using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry combined with star symbol patterns and partial least squares discriminant analysis (PLS-DA). Results: A total of 27 and 23 metabolites from the serum and urine of Fabry mice were distinguished from those of wild-type mice, respectively, based on p-value (<0.05) and variable importance in projection scores (>1.0) of PLS-DA. In the serum, metabolites of the glutathione, glutathione disulfide, citrulline, and kynurenine pathways that are related to oxidative stress, nitric oxide biosynthesis, and inflammation were increased, whereas those involved in pyruvate and tyrosine metabolism and the tricarboxylic acid cycle were altered in the 20- and 40-week-old urine of FD model mice. Conclusion: Altered metabolic signatures associated with disease progression by oxidative stress, inflammation, nitric oxide biosynthesis, and immune regulation in the early and late stages of FD.

Circulating osteoprotegerin as a cardiac biomarker for left ventricular diastolic dysfunction in patients with pre-dialysis chronic kidney disease: the KNOW-CKD study.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a major cause of mortality in patients with chronic kidney disease (CKD), and diagnosis is challenging. Moreover, no specific biomarker for HFpEF has been validated in patients with CKD. The present study aimed to investigate the association between serum osteoprotegerin (OPG) levels and the risk of left ventricular diastolic dysfunction (LVDD), a surrogate of HFpEF, in patients with pre-dialysis CKD. METHODS: A total of 2039 patients with CKD at stage 1 to pre-dialysis 5 were categorized into quartiles (Q1 to Q4) by serum OPG levels, and were cross-sectionally analyzed. The study outcome was LVDD, which was operationally defined as the ratio of early transmitral blood flow velocity to early diastolic velocity of the mitral annulus (E/e') > 14. RESULTS: In the analysis of baseline characteristics, higher serum OPG levels were clearly related to the risk factors of HFpEF. A scatter plot analysis revealed a moderate correlation between serum OPG levels and E/e' (R = 0.351, P < 0.001). Logistic regression analysis demonstrated that the risk of LVDD in Q3 (adjusted odds ratio 2.576, 95% confidence interval 1.279 to 5.188) and Q4 (adjusted odds ratio 3.536, 95% confidence interval 1.657 to 7.544) was significantly higher than that in Q1. CONCLUSIONS: Elevated serum OPG levels are associated with the risk of LVDD in patients with pre-dialysis CKD. The measurement of serum OPG levels may help the diagnosis of LVDD, which is an important echocardiographic feature of HFpEF.

Circulating osteoprotegerin levels and cardiovascular outcomes in patients with pre-dialysis chronic kidney disease: results from the KNOW-CKD study.

While the relationship between circulating osteoprotegerin (OPG) and cardiovascular events is well-established in the general population, its association with cardiovascular risks in chronic kidney disease (CKD) patients remains less robust. This study hypothesized that elevated circulating OPG levels might be associated with an increased risk of major adverse cardiac events (MACE) in CKD patients, a total of 2,109 patients with CKD stages 1 through pre-dialysis 5 from the KNOW-CKD cohort were categorized into quartiles based on serum OPG levels. The primary outcome of the study was 3-point MACE, defined as a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiac death. The median follow-up duration was 7.9 years. The cumulative incidence of 3-point MACE significantly varied across serum OPG levels in Kaplan-Meier curve analysis (P < 0.001, log-rank test), with the highest incidence observed in the 4th quartile. Cox regression analysis indicated that, relative to the 1st quartile, the risk of 3-point MACE was significantly higher in the 3rd (adjusted hazard ratio 2.901, 95% confidence interval 1.009 to 8.341) and the 4th quartiles (adjusted hazard ratio 4.347, 95% confidence interval 1.410 to 13.395). In conclusion, elevated circulating OPG levels are associated with adverse cardiovascular outcomes in pre-dialysis CKD patients.

Insulin resistance is associated with incident chronic kidney disease in population with normal renal function.

Background: Insulin resistance is prevalent in chronic kidney disease and may accelerate the progression of chronic kidney disease. This study aimed to investigate whether insulin resistance is associated with the development of incident chronic kidney disease in a population with normal renal function. Methods: A total of 3,331 participants from a community-based cohort with normal renal function were prospectively analyzed. We determined the relationship of insulin resistance indices with the incident chronic kidney disease using the Cox proportional hazard model and Kaplan-Meier survival analysis. Results: During a mean follow-up of 11.03 ± 4.22 years, incident chronic kidney disease occurred in 414 participants (12.4%). The high homeostasis model assessment-insulin resistance level group had an increased risk of incident chronic kidney disease (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.13-1.74; p = 0.002) compared to the normal group after adjustment for age, sex, history of hypertension, body mass index, total cholesterol, alcohol drinking status, smoking status, and baseline estimated glomerular filtration rate. The risk of incident chronic kidney disease also increased with the lower quantitative insulin sensitivity check index level (HR, 0.62; 95% CI, 0.41-0.92; p = 0.02) and higher leptin-adiponectin ratio level (HR, 1.23; 95% CI, 1.06-1.42; p = 0.006). Conclusion: Higher insulin resistance indices are associated with the incidence of chronic kidney disease. Our data suggest that increased insulin resistance may be involved in the development of incident chronic kidney disease in a population with normal renal function.

Fatal Hypermagnesemia in Patients Taking Magnesium Hydroxide.

Hypermagnesemia is a rare but potentially fatal electrolyte disorder often overlooked because of its unfamiliarity. Magnesium is regulated through a balance of bone, intestinal absorption, and renal excretion. Hypermagnesemia typically arises from excessive magnesium intake or reduced renal excretion; however, it also occurs in patients with normal kidney function. Herein, we report two cases of hypermagnesemia in patients taking magnesium hydroxide for constipation. The first case involved an 82-year-old woman with end-stage renal disease who developed metabolic encephalopathy due to hypermagnesemia, after taking 3,000 mg of magnesium hydroxide daily for constipation. Her magnesium level was 9.9 mg/dL. Her treatment involved discontinuing magnesium hydroxide and continuing hemodialysis, which led to her recovery. In the second case, a 50-year-old woman with a history of cerebral hemorrhage and mental retardation developed hypermagnesemia despite having normal renal function. She was also taking magnesium hydroxide for constipation, and her magnesium level was 11.0 mg/dL. She experienced cardiac arrest while preparing for continuous renal replacement therapy (CRRT). After achieving return of spontaneous circulation, CRRT was initiated, and her magnesium level showed a decreasing trend. However, vital signs and lactate levels did not recover, leading to death. These cases highlight the importance of prompt diagnosis and intervention for hypermagnesemia and the need to regularly monitor magnesium levels in individuals receiving magnesium-containing preparations, especially those with impaired kidney function.

Prognostic role of the neutrophil-to-lymphocyte ratio in patients with chronic kidney disease.

BACKGROUND/AIMS: The neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in cardiovascular disease, infection, inflammatory disease, and several malignancies. Therefore, the NLR has a possible predictive value in patients with chronic kidney disease (CKD), but this predictive value has not been validated. Here, we aimed to investigate the possibility of NLR as a predictor of CKD progression. METHODS: This retrospective observational study included 141 patients with non-dialysis CKD. The participants were divided into terciles (T1, T2, and T3) according to NLR. The primary outcome was defined as a composite kidney event, which included a decline in the estimated glomerular filtration rate (eGFR) of at least 50% or initiation of renal replacement therapy during the follow-up period. RESULTS: The mean follow-up duration was 5.45 ± 2.11 years. The mean NLRs were 1.35 ± 0.05 in T1 (n = 47), 2.16 ± 0.04 in T2 (n = 47), and 4.29 ± 0.73 in T3 (n = 47). The group with the highest NLR (T3) had higher baseline CKD and serum creatinine and lower eGFR levels than the group with the lowest NLR (T1). The cumulative incidence rate of composite kidney events was significantly higher in T3 compared with T1 (p < 0.001, log-rank test). Cox regression analysis revealed that high NLR was associated with the risk of composite kidney events (adjusted hazard ratio, 3.33; 95% confidence interval, 1.43-7.76). CONCLUSION: A higher NLR reflects the more advanced stage of CKD and suggests a role for NLR as a biomarker for predicting CKD progression.

Uncontrolled hypertension is associated with increased risk of graft failure in kidney transplant recipients: a nationwide population-based study.

Backgroud: Hypertension is highly prevalent in patients with kidney transplantation caused by transplantation-related immunologic or non-immunologic risk factors. However, whether a strict definition of hypertension (≥130/80 mmHg) and subdivided blood pressure (BP) groups are associated with an increased risk of graft failure after kidney transplantation using a nationwide large cohort study are still unknown. Methods: Using Korean National Health Insurance Service data, we included 14,249 patients who underwent kidney transplantation from 2002 to 2016. Patients were categorized into five BP groups according to the 2021 Kidney Disease: Improving Global Outcomes practice guidelines for BP management: normal BP (<120/80 mmHg), elevated BP (120-129/ < 80 mmHg), incident hypertension (≥130/80 mmHg), and controlled or uncontrolled hypertension with anti-hypertensive medications. Results: The primary outcome was graft failure, which occurred in 1934 (13.6%) participants during the 6-year follow-up. After adjusting for covariates, hypertension was associated with a higher risk of graft failure [Adjusted hazard ratio (AHR), 1.70; 95% confidence interval (CI), 1.48-1.96)] than no-hypertension. The AHR for graft failure was the highest in patients with uncontrolled hypertension (AHR, 2.13; 95% CI, 1.80-2.52). The risk of graft failure had a linear relationship with systolic and diastolic BP, and pulse pressure. Conclusions: In this nationwide population-based study, hypertension ≥130/80 mmHg based on the 2021 KDIGO BP guidelines in kidney transplantion recipients, and elevated systolic and diastolic BP, and pulse pressure were associated with the risk of developing graft failure in kidney transplant recipients.

Underweight status and development of end-stage kidney disease: A nationwide population-based study.

BACKGROUND: Underweight status increases the risk of cardiovascular disease and mortality in the general population. However, whether underweight status is associated with an increased risk of developing end-stage kidney disease is unknown. METHODS: A total of 9 845 420 participants aged ≥20 years who underwent health checkups were identified from the Korean National Health Insurance Service database and analysed. Individuals with underweight (body mass index [BMI] < 18.5 kg/m2 ) and obesity (BMI ≥ 25 kg/m2 ) were categorized according to the World Health Organization recommendations for Asian populations. RESULTS: During a mean follow-up period of 9.2 ± 1.1 years, 26 406 participants were diagnosed with end-stage kidney disease. After fully adjusting for other potential predictors, the moderate to severe underweight group (<17 kg/m2 ) had a significantly higher risk of end-stage kidney disease than that of the reference (normal) weight group (adjusted hazard ratio, 1.563; 95% confidence interval, 1.337-1.828), and competing risk analysis to address the competing risk of death also showed the similar results (adjusted hazard ratio, 1.228; 95% confidence interval, 1.042-1.448). Compared with that of the reference BMI group (24-25 kg/m2 ), the adjusted hazard ratios for end-stage kidney disease increased as the BMI decreased by 1 kg/m2 . In the sensitivity analysis, sustained underweight status or progression to underweight status over two repeated health checkups, when compared with normal weight status, had a higher hazard ratio for end-stage kidney disease. CONCLUSIONS: Underweight status is associated with an increased risk of end-stage kidney disease, and this association gradually strengthens as BMI decreases.

Risk of Hyponatremia after Tramadol/Acetaminophen Single-Pill Combination Therapy: A Real-World Study Based on the OMOP-CDM Database.

BACKGROUND AND OBJECTIVE: Tramadol has been reported to cause hyponatremia but the evidence is conflicting. The risk of hyponatremia resulting from combination oral tramadol/acetaminophen (TA) therapy is thus unknown. This study examined whether, compared with acetaminophen (AA), TA use is associated with an increased risk of hyponatremia. METHODS: Hospital data compatible with the Observational Medical Outcomes Partnership-Common Data Model (OMOP-CDM; version 5.3) for 30,999 patients taking TA or AA from 2011 through 2020 were analyzed. New-onset hyponatremia was defined as a serum sodium level < 135 mEq/L within 10 days after drug initiation. The incidence rate ratio was calculated based on crude and 1:1 propensity-score-matched models. Subgroup analyses compared patients taking TA extended-release (TA-ER) and TA immediate-release (TA-IR) formulations. RESULTS: Among the 30,999 patients, 12,122 (39.1%) were aged > 65 years and 16,654 (53.7%) were male. Hyponatremia within 10 days developed in 1613 (8.4%) of the 19,149 patients in the TA group; the incidence rate was higher than in the AA group (4.2%; 493 out of 11,850 cases). In the propensity-score-matched model, the incidence rate of hyponatremia in the TA group was 6.8 per 1000 person-days (PD), which was 1.57-fold (1.31, 1.89) higher than that in the AA group (4.3 per 1000 PD). In both the crude and propensity-score-matched models, the incidence rate of hyponatremia was significantly higher in the TA-ER than TA-IR subgroup. CONCLUSION: In this real-world study, hyponatremia was more frequently observed in the TA than AA group, and in the TA-ER than TA-IR subgroup. Therefore, it is imperative to prescribe tramadol cautiously and closely monitor electrolyte levels.

Urinary Phosphorus Excretion and Cardiovascular Outcomes in Patients with Pre-Dialysis Chronic Kidney Disease: The KNOW-CKD Study.

The relationship between 24-h urinary phosphorus excretion (24 h UPE) and cardiovascular disease in patients with pre-dialysis chronic kidney disease (CKD) has rarely been studied, despite the fact that the relationship between serum phosphorus level and the risk of a cardiovascular event is well established. A total of 1701 patients with pre-dialysis CKD were finally included for the analyses and were divided into tertiles by 24 h UPE (first tertile (T1, 349.557 (mean) ± 88.413 (standard deviation)), second tertile (T2, 557.530 ± 50.738), and third tertile (T3, 851.695 ± 171.593). The study outcome was a six-point major adverse cardiac event (MACE). The median follow-up duration was 7.992 years. Kaplan-Meier curve analysis visualized that the cumulative incidences of a six-point MACE (p = 0.029) significantly differed from 24 h UPE levels, as the incidence rate of the study outcomes was highest in T1 and lowest in T3. Cox proportional hazard models unveiled that, compared to T1, the risk of a six-point MACE was significantly decreased in T3 (adjusted hazard ratio (HR) 0.376, 95% confidence interval (CI) 0.207 to 0.683). The restricted cubic spline curve analysis visualized an inverted S-shaped association between 24 h UPE level and the risk of a six-point MACE, indicating a significantly increased risk of a six-point MACE in patients with a low 24 h UPE level. In conclusion, low 24 h UPE is associated with adverse cardiovascular outcomes in patients with CKD. Our finding emphasizes that low 24 h UPE should not be a reliable marker for dietary restriction of phosphorus that essentially leads to better outcomes in patients with CKD.

The effects of socioeconomic status on major adverse cardiovascular events: a nationwide population-based cohort study.

BACKGROUND: Although multiple factors influence the risk of major adverse cardiovascular events (MACE), the effects of socioeconomic status on MACE in the presence and absence of renal dysfunction (RD) have not been comprehensively explored in Korea. METHODS: We examined the effects of socioeconomic status on MACE in individuals with and without RD. The data of 44,473 Koreans from 2008 to 2017 were obtained from the Health Care Big Data Platform of the Ministry of Health and Welfare in Korea. Their socioeconomic status was assessed using a socioeconomic score (SES) based on marital status, education, household income, and occupation. The incidence of myocardial infarction (MI), stroke, and death was compared according to SES level (0-4). Multiple linear regression analysis was used to evaluate the hazard ratios and 95% confidence intervals for outcomes based on participant SES. RESULTS: MI risk was only affected by education level. The participants' income, education, and SES affected their stroke risk, whereas death was associated with all four socioeconomic factors. The incidence of stroke and death increased as SES worsened (from 0 to 4). SES was positively related to risk of stroke and death in participants without RD. SES did not affect MI, stroke, or death in participants with RD. CONCLUSION: A low socioeconomic status is associated with risk of stroke and death, especially in individuals without RD.

Association between urinary chloride excretion and progression of coronary artery calcification in patients with nondialysis chronic kidney disease: results from the KNOW-CKD study.

BACKGROUND: Urine chloride has recently been suggested as a biomarker of renal tubule function in patients with nondialysis chronic kidney disease (CKD), as low urinary chloride concentration is associated with an increased risk of CKD progression. We investigate the association between urinary chloride excretion and the progression of coronary artery calcification (CAC). METHODS: A total of 1,065 patients with nondialysis CKD were divided into tertiles by spot urine chloride-to-creatinine ratios. The 1st, 2nd, and 3rd tertiles were defined as low, moderate, and high urinary chloride excretion, respectively. The study outcome was CAC progression, which was defined as an increase in coronary artery calcium score of more than 200 Agatston units during the 4-year follow-up period. RESULTS: Compared to moderate urinary chloride excretion, high urinary chloride excretion was associated with decreased risk of CAC progression (adjusted odds ratio, 0.379; 95% confidence interval, 0.190-0.757), whereas low urinary chloride excretion was not associated with risk of CAC progression. Restricted cubic spine depicted an inverted J-shaped curve, with a significant reduction in the risk of CAC progression in subjects with high spot urine chloride-to-creatinine ratios. CONCLUSION: High urinary chloride excretion is associated with decreased risk of CAC progression in patients with nondialysis CKD.

Bone Mineral Density and All-Cause Mortality in Patients with Nondialysis Chronic Kidney Disease: Results from KNOW-CKD Study.

Despite the clear association between low BMD and all-cause mortality in the general population, the association has not been validated in patients with nondialysis CKD. To investigate the association of low BMD with all-cause mortality in this population, a total of 2089 patients with nondialysis CKD at stages 1 to predialysis 5 were categorized into normal BMD (T-score ≥ -1.0), osteopenia (-2.5 < T-score < -1.0), and osteoporosis (T-score ≤ - 2.5) by the BMD at femoral neck. The study outcome was all-cause mortality. Kaplan-Meier curve depicted a significantly increased number of all-cause death events in the subjects with osteopenia or osteoporosis during the follow-up period compared with subjects with normal BMD. Cox regression models demonstrated that osteoporosis, but not osteopenia, was significantly associated with an increased risk of all-cause mortality (adjusted hazard ratio 2.963, 95% confidence interval 1.655 to 5.307). Smoothing curve fitting model visualized a clear inverse correlation between BMD T-score and the risk of all-cause mortality. Even after recategorizing the subjects by BMD T-scores at total hip or lumbar spine, the result was similar to the primary analyses. Subgroup analyses revealed that the association was not significantly modified by clinical contexts, such as age, gender, body mass index, estimated glomerular filtration rate, and albuminuria. In conclusion, low BMD is associated with an increased risk of all-cause mortality in patients with nondialysis CKD. This emphasizes that the routine measurement of BMD by DXA may confer an additional benefit beyond the prediction of fracture risk in this population.

Rheumatoid arthritis and the risk of end-stage renal disease: A nationwide, population-based study.

Introduction: Despite the risk of incident chronic kidney disease among the patients with rheumatoid arthritis (RA), the association of RA and the risk of end-stage renal disease (ESRD) has not been clearly elucidated. We aimed to investigate the association of RA and the risk of ESRD. Materials and methods: A total of 929,982 subjects with (n = 154,997) or without (n = 774,985) RA from the National Health Insurance Service (NHIS) database in Koreas (corresponding to the period between 2009 and 2017) were retrospectively analyzed. RA was defined by the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM), codes plus any dispensing of disease-modifying anti-rheumatic drugs. The primary outcome was incident ESRD, identified by a combination of the ICD-10-CM codes and a special code assigned to patients receiving maintenance dialysis for ≥ 3 months or those with a transplant kidney. Results: Compared to the subjects without RA, the subjects with RA resulted in an increased incidence of ESRD (incidence rates of 0.374 versus 0.810 cases per 1,000 person-years). Accordingly, compared to the subjects without RA, the risk of ESRD was significantly increased among the subjects with RA (adjusted hazard ratio 2.095, 95% confidence interval 1.902-2.308). Subgroup analyses revealed that the risk of ESRD imposed by RA is relatively higher in relatively young and healthy individuals. Conclusion: Rheumatoid arthritis (RA) increase the risk of ESRD. As the risk of ESRD imposed by RA is relatively higher in relatively young and healthy individuals, kidney-protective treatment, such as biologic agents, should be preferentially considered among these patients with RA.

Weight change and risk of depression in patients with diabetic kidney disease: a nationwide population-based study.

BACKGROUND: Several studies have reported that depression is prevalent in patients with diabetes or chronic kidney disease. However, the relationship between weight changes and the risk of depression has not been elucidated in patients with diabetic kidney disease (DKD). METHODS: From the Korean National Health Insurance Service database, we selected 67,866 patients with DKD and body weight data from two consecutive health examinations with a 2-year interval between 2009 and 2012. Weight change over 2 years was categorized into five groups: ≥-10%, <-10% to ≥-5%, <-5% to <5%, ≥5% to <10%, and ≥10%. The occurrence of depression was monitored via the codes of International Statistical Classification of Diseases, 10th revision through the end of 2018. RESULTS: During the 5.24-year follow-up, 17,023 patients with DKD developed depression. Weight change and the risk of depression had a U-shaped relationship: patients with ≥-10% weight change (hazard ratio [HR], 1.12) and those with ≥10% weight change (HR, 1.11) showed higher HRs for depression than those with <-5% to <5% weight change, even after adjusting for several confounding factors. In the subgroup analyses, the risk of depression tended to increase as weight gain or weight loss increased in all subgroups. CONCLUSION: Both weight loss and weight gain increased the risk of depression in patients with DKD.

Serum triglycerides level is independently associated with renal outcomes in patients with non-dialysis chronic kidney disease: Results from KNOW-CKD study.

To investigate whether high serum triglycerides (TG) level is associated with adverse renal outcomes in patients with non-dialysis chronic kidney disease (CKD), a total of 2,158 subjects from a prospective cohort study (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were divided into the quartile by serum TG level. The primary outcomes were composite renal events, which is defined as a composite of decline of kidney function (the first occurrence of > 50% decline of estimated glomerular filtration rate or doubling of serum creatinine from the baseline) or onset of end-stage renal disease (initiation of dialysis or kidney transplantation). During the median follow-up of 6.940 years, the cumulative incidence of composite renal event was significantly differed by serum TG level in Kaplan-Meier curve analysis (P < 0.001, by Log-rank test). Cox regression analysis demonstrated that, compared to that of the 1st quartile, the risk of composite renal event was significantly higher in the 4th quartile (adjusted hazard ratio 1.433, 95% confidence interval 1.046 to 1.964). The association between high serum TG level and adverse renal outcome remained consistent in the cause-specific hazard model. Subgroup analyses revealed that the association is modified by age, estimated glomerular filtration rate, and spot urine albumin-to-creatinine ratio. In conclusion, high serum TG level is independently associated with adverse renal outcomes in patients with non-dialysis CKD. Interventional studies are warranted to determine whether lowering serum TG levels may alter the natural course of CKD.

Non-High-Density Lipoprotein Cholesterol and Progression of Chronic Kidney Disease: Results from the KNOW-CKD Study.

As the relation between serum non-high-density lipoprotein cholesterol (nHDL) level and renal outcomes has never been investigated in patients with non-dialysis chronic kidney disease (CKD) yet, we here aimed to unveil the association of nHDL with CKD progression. A total of 2152 patients with non-dialysis CKD at stages 1 to 5 from the KNOW-CKD study were categorized into the tertile (i.e., 1st (T1), 2nd (T2), and 3rd (T3) tertiles) by nHDL, and were prospectively analyzed. The primary outcome was the composite renal event, defined as a composite of decline of kidney function or onset of end-stage renal disease. Kaplan-Meier survival curves analysis demonstrated that the cumulative incidence of the composite renal event was significantly increased in T1 and T3, compared to T2 (p = 0.028, by Log-rank test). Cox regression analysis revealed that both T1 (adjusted hazard ratio 1.309, 95% confidence interval 1.074-1.595) and T3 (adjusted hazard ratio 1.272, 95% confidence interval 1.040-1.556) are associated with significantly increased risk of a composite renal event, compared to T2. The restricted cubic spline plot demonstrated a non-linear, U-shaped association between nHDL and the risk of a composite renal event. In conclusion, both low and high serum nHDL levels are associated with increased risk of CKD progression.

Non-High-Density Lipoprotein Cholesterol and Cardiovascular Outcomes in Chronic Kidney Disease: Results from KNOW-CKD Study.

As non-high-density lipoprotein cholesterol (non-HDL-C) levels account for all atherogenic lipoproteins, serum non-HDL-C level has been suggested to be a marker for cardiovascular (CV) risk stratification. Therefore, to unveil the association of serum non-HDL-C levels with CV outcomes in patients with non-dialysis chronic kidney disease (ND-CKD), the patients at stages 1 to 5 (n = 2152) from the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD) were prospectively analyzed. The subjects were divided into quintiles by serum non-HDL-C level. The primary outcome was a composite of all-cause death or non-fatal CV events. The median duration of follow-up was 6.940 years. The analysis using the Cox proportional hazard model unveiled that the composite CV event was significantly increased in the 5th quintile (adjusted hazard ratio 2.162, 95% confidence interval 1.174 to 3.981), compared to that of the 3rd quintile. A fully adjusted cubic spline model depicted a non-linear, J-shaped association between non-HDL-C and the risk of a composite CV event. The association remained robust in a series of sensitivity analyses, including the analysis of a cause-specific hazard model. Subgroup analyses reveled that the association is not significantly altered by clinical conditions, including age, gender, body mass index, estimated glomerular filtration rate, and albuminuria. In conclusion, high serum non-HDL-C level increased the risk of adverse CV outcomes among the patients with ND-CKD. Further studies are warranted to define the optimal target range of non-HDL-C levels in this population.