Relationship between urinary potassium excretion, serum potassium levels and cardiac injury in non-dialysis chronic kidney disease: KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD).

Although the cardiovascular benefits of an increased urinary potassium excretion have been suggested, little is known about the potential cardiac association of urinary potassium excretion in patients with chronic kidney disease. In addition, whether the cardiac association of urinary potassium excretion was mediated by serum potassium levels has not been studied yet. We reviewed the data of 1633 patients from a large-scale multicentre prospective Korean study (2011-2016). Spot urinary potassium to creatinine ratio was used as a surrogate for urinary potassium excretion. Cardiac injury was defined as a high-sensitivity troponin T ≥ 14 ng/l. OR and 95 % (CI for cardiac injury were calculated using logistic regression analyses. Of 1633 patients, the mean spot urinary potassium to creatinine ratio was 49·5 (sd 22·6) mmol/g Cr and the overall prevalence of cardiac injury was 33·9 %. Although serum potassium levels were not associated with cardiac injury, per 10 mmol/g Cr increase in the spot urinary potassium to creatinine ratio was associated with decreased odds of cardiac injury: OR 0·917 (95 % CI 0·841, 0·998), P = 0·047) in multivariate logistic regression analysis. In mediation analysis, approximately 6·4 % of the relationship between spot urinary potassium to creatinine ratio and cardiac injury was mediated by serum potassium levels, which was not statistically significant (P = 0·368). Higher urinary potassium excretion was associated with lower odds of cardiac injury, which was not mediated by serum potassium levels.

Polypharmacy and the Progression of Chronic Kidney Disease: Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease.

INTRODUCTION: The renal hazard of polypharmacy has never been evaluated in predialysis chronic kidney disease (CKD) patients. OBJECTIVE: We aimed to analyze the renal hazard of polypharmacy in predialysis CKD patients with stage 1-5. METHOD: The data of 2,238 patients from a large-scale multicenter prospective Korean study (2011-2016), excluding 325 patients with various missing data, were reviewed. Polypharmacy was defined as taking 6 or more medications at the time of enrollment; renal events were defined as a ≥50% decrease in kidney function from baseline values, doubling of the serum creatinine levels, or initiation of renal replacement treatment. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox proportional-hazard regression analysis. RESULTS: Of the 1,913 patients, the mean estimated glomerular filtration rate was 53.6 mL/min/1.73 m2. The mean medication count was 4.1, and the prevalence of polypharmacy was 27.1%. During the average period of 3.6 years, 520 patients developed renal events (27.2%). Although increased medication counts were associated with increased renal hazard with HR (95% CI) of 1.056 (1.007-1.107, p = 0.025), even after adjusting for various confounders, adding comorbidity score and kidney function nullified the statistical significance. In mediation analysis, 55.6% (p = 0.016) of renal hazard in increased medication counts was mediated by the kidney function, and there was no direct effect of medication counts on renal event development. In subgroup analysis, the renal hazard of the medication counts was evident only in stage 1-3 of CKD patients (p for interaction = 0.014). CONCLUSIONS: We cannot identify the direct renal hazard of multiple medications, and most of the potential renal hazard was derived from intimate relationship with disease burden and kidney function.

Association between insulin resistance and lung function trajectory over 4 years in South Korea: community-based prospective cohort.

BACKGROUND: Hyperglycemic conditions are associated with respiratory dysfunction. Although several studies have reported that insulin resistance (IR) is related to decreased lung function, the association between IR and change in lung function has been rarely studied. This study aimed to investigate the potential association of IR on annual change in lung function using a community-based prospective cohort in Korea. METHODS: We selected 4827 Korean participants whose serial lung functions were assessed over 4 years using 1:3 propensity score matching. Exposure was baseline IR estimated with homeostatic model assessment (HOMA-IR), and outcomes were annual changes in lung function determined by calculating the regression coefficient using least-square linear regression analysis. RESULTS: In the multivariate linear regression, per one unit increased log transformed HOMA-IR was associated with decline in FEV1%-predicted (ß: - 0.23, 95% CI: - 0.36 to - 0.11) and FVC %-predicted (ß: - 0.20, 95% CI: - 0.33 to - 0.08), respectively. In the generalized additive model plot, HOMA-IR showed a negative linear association with annual changes in FEV1%-predicted and FVC %-predicted. The suggested threshold of HOMA-IR for decline in lung function was 1.0 unit for annual change in FEV1%-predicted and 2.2 unit for annual change in FVC %-predicted. Age showed statistically significant effect modification on the relationship between HOMA-IR and annual change in FEV1%-predicted. Increased HOMA-IR was associated with the decreased annual change in FEV1%-predicted, particularly in older people. CONCLUSIONS: In South Korea, increased HOMA-IR was associated with decline in lung function. Since IR was related to decline in FEV1%-predicted, particularly in older people, tailored approaches are needed in these populations. The potential pulmonary hazard of IR needs to be confirmed in future studies.

Hepcidin, iron indices and bone mineral metabolism in non-dialysis chronic kidney disease.

BACKGROUND: Few studies have examined the association between hepcidin, iron indices and bone mineral metabolism in non-dialysis chronic kidney disease (CKD) patients. METHODS: We reviewed the data of 2238 patients from a large-scale multicenter prospective Korean study (2011-16) and excluded 214 patients with missing data on markers and related medications of iron and bone mineral metabolism, hemoglobin, blood pressure and causes of CKD. Multivariate linear regression analysis was used to identify the association between iron and bone mineral metabolism. RESULTS: The proportion of CKD Stages 1-5 were 16.2, 18.7, 37.1, 21.6 and 6.4%, respectively. Per each 10% increase in transferrin saturation (TSAT), there was a 0.013 mmol/L decrease in phosphorus [95% confidence interval (CI) -0.021 to -0.004; P = 0.003] and a 0.022 nmol/L increase in logarithmic 25-hydroxyvitamin D (Ln-25OHD) levels (95% CI 0.005-0.040; P = 0.019). A 1 pmol/L increase in Ln-ferritin was associated with a 0.080 ng/L decrease in Ln-intact parathyroid hormone (Ln-iPTH; 95% CI -0.122 to -0.039; P < 0.001). Meanwhile, beta (95% CI) per 1 unit increase in phosphorus, Ln-25OHD and Ln-iPTH for the square root of the serum hepcidin were 0.594 (0.257-0.932; P = 0.001), -0.270 (-0.431 to -0.108; P = 0.001) and 0.115 (0.004-0.226; P = 0.042), respectively. In subgroup analysis, the relationship between phosphorus, 25OHD and hepcidin was strongest in the positive-inflammation group. CONCLUSIONS: Markers of bone mineral metabolism and iron status, including hepcidin, were closely correlated to each other. Potential mechanisms of the relationship warrant further studies.

Relationship between Thyroid and Kidney Function: Analysis from the Korea National Health and Nutrition Examination Survey Between 2013 and 2015.

INTRODUCTION: Thyroid function is evaluated by thyroid stimulating hormone (TSH) and free thyroxine (fT4). Although many studies have indicated an intimate relationship between thyroid hormones and kidney functions, reports about the simultaneous evaluation of TSH and fT4 are rare. OBJECTIVE: We aimed to analyze the association between TSH and kidney function, with emphasis on a potential nonlinear relationship, and identify an independent relationship between fT4 and kidney function. METHODS: We reviewed the data of 7,061 subjects in the Korea National Health and Nutrition Examination Surveys who were randomly subsampled for thyroid function evaluation between 2013 and 2015. A total of 5,578 subjects were included in the final analysis, after excluding people <18 years old, and those with a short fasting time, abnormal fT4 levels, and thyroid disease or related medications. Creatinine-based estimated glomerular filtration rate (eGFR) was used to define kidney function. RESULTS: A 1 mmol/L increase of logarithmic TSH was associated with decreased eGFR (ß: -1.8; 95% CI -2.3 to -1.2; p < 0.001), according to multivariate linear regression analysis. On the multivariate generalized additive model plot, TSH demonstrated an L-shaped relationship with eGFR, showing a steeper slope for 0-4 mIU/L of TSH. A 1 µg/dL increase of fT4 was also associated with decreased eGFR (ß: -7.0; 95% CI -0.94 to -4.7; p < 0.001) on the multivariate linear regression analysis; this association was reversed after adjusting for age. On the mediation analysis, the indirect effect via age and direct effect per 1 µg/dL increase of fT4 on eGFR was 9.9 (8.1 to 11.7, p < 0.001) and -7.1 (-9.3 to -4.8, p < 0.001), respectively. CONCLUSIONS: Increased TSH was associated with decreased eGFR, particularly in the reference range. The direct effect of increased fT4 was decreased eGFR, which may be affected indirectly by age.

Relationship between Cardiac Geometry and Serum Hepcidin in Chronic Kidney Disease: Analysis from the KNOW-CKD Study.

BACKGROUND: Few studies have examined the relationship between cardiac function and geometry and serum hepcidin levels in patients with chronic kidney disease (CKD). We aimed to identify the relationship between cardiac function and geometry and serum hepcidin levels. METHODS: We reviewed data of 1,897 patients in a large-scale multicenter prospective Korean study. Logistic regression analysis was used to identify the relationship between cardiac function and geometry and serum hepcidin levels. RESULTS: The mean relative wall thickness (RWT) and left ventricular mass index (LVMI) were 0.38 and 42.0 g/m2.7, respectively. The mean ejection fraction (EF) and early diastolic mitral inflow to annulus velocity ratio (E/e') were 64.1% and 9.9, respectively. Although EF and E/e' were not associated with high serum hepcidin, RWT and LVMI were significantly associated with high serum hepcidin levels in univariate logistic regression analysis. In multivariate logistic regression analysis after adjusting for variables related to anemia, bone mineral metabolism, comorbidities, and inflammation, however, only each 0.1-unit increase in RWT was associated with increased odds of high serum hepcidin (odds ratio, 1.989; 95% confidence interval, 1.358-2.916; P < 0.001). In the subgroup analysis, the independent relationship between RWT and high serum hepcidin level was valid only in women and patients with low transferrin saturation (TSAT). CONCLUSION: Although the relationship was not cause-and-effect, increased RWT was independently associated with high serum hepcidin, particularly in women and patients with low TSAT. The relationship between cardiac geometry and serum hepcidin in CKD patients needs to be confirmed in future studies.

Self-rated health and the risk of incident chronic kidney disease: a community-based Korean study.

BACKGROUND: The relationship between self-rated health (SRH) and the development of incident chronic kidney disease (CKD) has not been explored in the general population. METHODS: We reviewed the data of 7027 participants in the Ansung-Ansan cohort study. SRH was categorized as poor, fair, or good, and the outcome was the development of CKD, defined as the first event of an estimated glomerular filtration rate < 60 mL/min/1.73 m2, at least twice during the follow-up period. Hazard ratios (HRs) and confidence intervals (CIs) were calculated using Cox proportional hazards regression analysis. RESULTS: Over a mean follow-up duration of 11.9 years, 951 participants (13.5%) developed CKD. Compared with poor self-rated health, the HR (95% CI) of fair self-rated health for incident CKD development was 0.771 (0.657-0.905; P = 0.001), whereas that of good self-rated health was 0.795 (0.676-0.935; P = 0.006). However, the renal hazard of good self-rated health did not differ from that of fair self-rated health. In the fully adjusted model, the HR (95% CI) of poor self-rated health compared to non-poor self-rated health for incident CKD was 1.278 (1.114-1.465, P < 0.001). Old age, smoking, cardiovascular disease, diabetes, hypertension, impaired sleep, and high levels of C-reactive protein and white blood cell counts were associated with increased odds of poor self-rated health, whereas male sex, college graduate level of education, and alcohol consumption were associated with decreased odds of poor self-rated health. CONCLUSION: Poor self-rated health is independently associated with CKD development. Therefore, the early detection of potential CKD patients through a brief questionnaire assessment may help control the incidence of CKD.

Risk of Chronic Kidney Disease Associated With Orthostatic Hypotensive Stress: A Community-Based Korean Study.

BACKGROUND: The relationship between orthostatic blood pressure (BP) changes and incident chronic kidney disease (CKD) has not been explored in Asian populations. METHODS: We reviewed the data of 7,039 participants from the Ansung-Ansan cohort study. BP was measured in the supine position and 2 minutes after standing. The change in BP from the supine to upright position was defined as orthostatic BP change. Orthostatic systolic BP (SBP) decline was defined as an orthostatic SBP change of <-2 mm Hg. The primary outcome was the development of CKD, defined as the first event of an estimated glomerular filtration rate <60 ml/min/1.73 m2 at least twice during the follow-up period. RESULTS: Of 7,039 participants, 949 (13.5 %) developed incident CKD over a mean of 11.9 years. Although orthostatic diastolic BP change was not associated with incident CKD, every 1 mm Hg increase in orthostatic SBP change was associated with a decreased risk of incident CKD (HR, 0.989; 95% CI, 0.982-0.995; P = 0.001). Orthostatic SBP decline was associated with an increased risk of incident CKD (HR, 1.337; 95% CI, 1.163-1.537; P < 0.001). Older age and diabetes were associated with increased odds of orthostatic SBP decline, whereas male sex and high body mass index were associated with decreased odds of orthostatic SBP decline. Subgroup analysis revealed that orthostatic SBP decline was associated with incident CKD only in non-diabetic participants. CONCLUSIONS: Orthostatic SBP decline was independently associated with an increased risk of future incident CKD, whereas orthostatic DBP decline was not.

Obstructive spirometry pattern and the risk of chronic kidney disease: analysis from the community-based prospective Ansan-Ansung cohort in Korea.

OBJECTIVE: There have been limited studies on the relationship between obstructive spirometry pattern and the development of chronic kidney disease (CKD). We investigated the association between obstructive spirometry pattern and incident CKD development in a large-scale prospective cohort study. METHODS: We reviewed the data of 7960 non-CKD adults aged 40-69 years who participated in the Ansung-Ansan cohort, a prospective community-based cohort study. Prebronchodilation results for the ratio of forced expiratory volume per 1 s (FEV1) to forced vital capacity (FVC) were used as the primary exposure. The primary outcome was incident CKD, defined as the first event of an estimated glomerular filtration rate <60 mL/min/1.73 m2. HRs and 95% CIs were calculated using multivariate Cox proportional hazard regression analysis. RESULTS: Over a mean follow-up period of 11.7 years, incident CKD developed in 511 subjects (6.4%). An increase of 0.1 in FEV1/FVC was associated with a decreased risk of incident CKD (HR 0.76, 95% CI 0.68 to 0.84, p<0.001). Compared with the fourth quartile, the HR (95 % CI) of the first quartile of FEV1/FVC ratio was 1.81 (1.39 to 2.36, p<0.001). In the restricted cubic spline curve, the renal hazard associated with a decreased FEV1/FVC ratio was evident at FEV1/FVC values <0.80, showing a U-shaped relationship. In subgroup analysis, the renal hazard associated with a decreased FEV1/FVC ratio was particularly evident in people without metabolic syndrome (p for interaction=0.018). CONCLUSION: Decreased FEV1/FVC ratio was independently associated with an increased risk of incident CKD development, particularly in people without metabolic syndrome. Future studies need to be conducted to confirm these results.

Indexation of left ventricular mass to predict adverse clinical outcomes in pre-dialysis patients with chronic kidney disease: KoreaN cohort study of the outcome in patients with chronic kidney disease.

BACKGROUND: No study has compared the clinical impact of indexation of left ventricular mass (LVM) on adverse clinical outcomes in pre-dialysis patients with chronic kidney disease (CKD). METHODS: We reviewed 2,101 patients from a large-scale multi-center prospective study that gathered anthropometric and echocardiographic measurements and clinical outcomes. The LVM was indexed as body surface area (LVMI-BSA) and height raised to the power of 2.7 (LVMI-H2.7). The main outcomes were composite renal and cardiovascular events and all-cause mortality. Left ventricular hypertrophy (LVH) was defined as the highest sex-specific quartile of LVMI-BSA or LVMI-H2.7. RESULTS: During a mean period of 3.5 years, 692 patients developed composite outcomes (32.9%). The area under the curve at 5 year of LVM (60.6%) for composite outcome was smaller than that for LVMI-BSA (63.2%, P <0.001) and LVMI-H2.7 (63.4%, P <0.001). The hazard ratio (HR) and 95% confidence interval (CI) per one unit increase in LVM (g), LVMI-BSA (g/m2), and LVMI-H2.7 (g/m2.7) for composite outcomes were 1.004 (1.002-1.005, P <0.001), 1.011 (1.006-1.016, P <0.001), and 1.023 (1.012-1.035, P <0.001), respectively. Patients with LVH determined by LVMI-BSA and LVMI-H2.7 (HR 1.352, 95% CI 1.123-1.626, P = 0.001) and LVH determined by only LVMI-BSA (HR 1.908, 95% CI 1.233-2.953, P = 0.004) showed an independent increase in the risk of composite-outcome development, when compared with patients without LVH, according to LVMI-BSA and LVMI-H2.7. CONCLUSION: Indexation of LVM improved the prediction of adverse outcomes. BSA may be as useful as height2.7 in indexing of LVM for predicting adverse outcomes in pre-dialysis patients with CKD.

Effect of Dialysis on Aryl Hydrocarbon Receptor Transactivating Activity in Patients with Chronic Kidney Disease.

PURPOSE: Elevated aryl hydrocarbon receptor (AhR) transactivating (AHRT) activity and uremia in chronic kidney disease (CKD) may interact with each other, further complicating the disease course. In this study, we prospectively estimated serum AHRT activity using a highly sensitive cell-based AhR-dependent luciferase activity assay in CKD patients and compared differences therein according to treatment modality. MATERIALS AND METHODS: Patients undergoing peritoneal dialysis (PD) (n=22) and hemodialysis (HD) (n=38) and patients with pre-dialysis CKD stage IV or V (n=28) were included. AHRT activity and intracellular adenosine triphosphate (ATP) levels were measured. We performed a correlation analysis for AHRT activity, ATP levels, and various clinical parameters. RESULTS: AHRT activity and intracellular ATP levels were inversely correlated and differed according to treatment modalities. AHRT activity was higher in non-dialysis CKD patients than in patients undergoing dialysis and was higher in patients undergoing HD, compared to PD. AHRT activity decreased after HD treatment in HD patients. ATP levels were higher in healthy controls than in patients with pre-dialysis CKD and PD and were further decreased in patients with HD. We noted significant correlations between multiple clinical parameters associated with cardiovascular risk factors and AHRT activity. CONCLUSION: AHRT activity was elevated in CKD patients, while dialysis treatment reduced AHRT activity. Further studies are warranted to specify AHRT activity and to evaluate the precise roles thereof in patients with CKD.