Triglyceride-glucose index is an independent predictor of coronary artery calcification progression in patients with chronic kidney disease.

BACKGROUND: Coronary artery calcification (CAC) is highly prevalent in patients with chronic kidney disease (CKD) and is associated with major adverse cardiovascular events and metabolic disturbances. The triglyceride-glucose index (TyGI), a novel surrogate marker of metabolic syndrome and insulin resistance, is associated with CAC in the general population and in patients with diabetes. This study investigated the association between the TyGI and CAC progression in patients with CKD, which is unknown. METHODS: A total of 1,154 patients with CKD (grades 1-5; age, 52.8 ± 11.9 years; male, 688 [59.6%]) were enrolled from the KNOWCKD (KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease). The TyGI was calculated as follows: ln (fasting triglycerides × fasting glucose/2). Patients were classified into tertiles (low, intermediate, high) based on the TyGI. The primary outcome was annualized percentage change in CAC score [(percent change in CAC score + 1)12/follow-up months - 1] of ≥15%, defined as CAC progression. RESULTS: During the 4-year follow-up, the percentage of patients with CAC progression increased across TyGI groups (28.6%, 37.5%, and 46.2% in low, intermediate, and high groups, respectively; p < 0.001). A high TyGI was associated with an increased risk of CAC progression (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.14-3.88; p = 0.02) compared to the low group. Moreover, a 1-point increase in the TyGI was related to increased risk of CAC progression (OR, 1.55; 95% CI, 1.06-1.76; p = 0.02) after adjustment. CONCLUSION: A high TyGI may be a useful predictor of CAC progression in CKD.

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

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

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.

Intrarenal Renin-Angiotensin System Activation Alters Relationship Between Systolic Blood Pressure and Progression of Chronic Kidney Disease.

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.

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.

Rapid decline in kidney function is associated with rapid deterioration of health-related quality of life in chronic kidney disease.

This study aimed to evaluate changes in health-related quality of life (HRQOL) in patients with chronic kidney disease (CKD) according to decline in kidney function. HRQOL was assessed using the Short Form-36 questionnaire composed of a physical component summary (PCS) and mental component summary (MCS). Rapid decline in kidney function was defined as a decline in the estimated glomerular filtration rate (eGFR) of > 3 mL/min/1.73 m2/year. Rapid deterioration of HRQOL was defined a change in the HRQOL value greater than the median. Among 970 patients, 360 (37.1%) were in the rapid kidney function decline group. In 720 patients who were 1:1 propensity score-matched, the baseline eGFR was not significantly different between the non-rapid and rapid kidney function decline groups. Compared with the baseline PCS score, the 5-year PCS score decreased in the non-rapid and rapid kidney function decline groups. The 5-year MCS score significantly decreased in the rapid kidney function decline group alone. Rapid decline in kidney function was significantly associated with rapid deterioration of the PCS (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 1.07-2.05; P = 0.018) and MCS (OR: 1.89; 95% CI 1.36-2.62; P < 0.001) scores. Rapid decline in kidney function was associated with rapid deterioration of HRQOL in patients with 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.

Low Klotho/Fibroblast Growth Factor 23 Ratio Is an Independent Risk Factor for Renal Progression in Chronic Kidney Disease: Finding From KNOW-CKD.

Background: We aimed to evaluate soluble Klotho and circulating fibroblast growth factor 23 (FGF23) ratio as a risk factor for renal progression, cardiovascular (CV) events, and mortality in chronic kidney disease (CKD). Methods: We analyzed 2,099 subjects from a CKD cohort whose soluble Klotho and C-terminal FGF23 levels were measured at enrollment. The Klotho to FGF23 ratio was calculated as Klotho values divided by FGF23 values + 1 (hereinafter called the Klotho/FGF23 ratio). Participants were categorized into quartiles according to Klotho/FGF23 ratio. The primary outcome was renal events, defined as the doubling of serum creatinine, 50% reduction of estimated glomerular filtration rate from the baseline values, or development of end-stage kidney disease. The secondary outcomes consisted of CV events and death. Changes in CV parameters at the time of enrollment and during follow-up according to the Klotho/FGF23 ratio were also examined. Results: During the follow-up period of 64.0 ± 28.2 months, 735 (35.1%) and 273 (13.0%) subjects developed renal events and composite outcomes of CV events and death, respectively. After adjustment, the first (HR: 1.36; 95% CI: 1.08-1.72, P = 0.010) and second (HR: 1.45; 95% CI: 1.15-1.83, P = 0.002) quartiles with regard to the Klotho/FGF23 ratio showed elevated risk of renal events as compared to the fourth quartile group. There was no significant association between Klotho/FGF23 ratio and the composite outcome of CV events and death. The prevalence of left ventricular hypertrophy and vascular calcification was higher in the low Klotho/FGF23 ratio quartiles at baseline and at the fourth-year follow-up. Conclusions: Low Klotho/FGF23 ratio was significantly associated with increased renal events in the cohort of Korean predialysis CKD patients.

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

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

The Association between Health-Enhancing Physical Activity and Quality of Life in Patients with Chronic Kidney Disease: Propensity Score Matching Analysis.

We investigate the association between health-enhancing physical activity and the quality of life in patients with non-dialysis chronic kidney disease. We performed data analysis on 1618 of 2238 patients from 2011 to 2016, obtained from the KoreaN Cohort Study for Outcome in Patients with Chronic Kidney Disease (KNOW-CKD). Health-related quality of life was measured using the Korean version 1.3 of Kidney Disease Quality of Life short-form questionnaire. Health-enhancing physical activity was defined as 150 min of moderate-intensity or 75 min of vigorous-intensity aerobic physical activity throughout the week. Propensity score matching analysis and linear regression was performed to estimate the effect of health-enhancing physical activity on health-related quality of life. The estimate of average treatment effects was 2.60 in the kidney component summary score, 4.45 in the physical component summary score, and 4.24 in the mental component summary score. In all component summary scores and most of their subscales, health-enhancing physical activity showed a significant association with health-related quality of life. Subgroup and sensitivity analyses also showed robust results. This study suggests that health-enhancing physical activity elevated quality of life in patients with non-dialysis chronic kidney disease. The results can contribute to encourage physical activity in patients with chronic kidney disease.

Quality of life in patients with diabetic nephropathy: findings from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease) cohort.

BACKGROUND: Diabetic nephropathy (DN) can affect quality of life (QoL) because it requires arduous lifelong management. This study analyzed QoL differences between DN patients and patients with other chronic kidney diseases (CKDs). METHODS: The analysis included subjects (n = 1,766) from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease) cohort who completed the Kidney Disease Quality of Life Short Form questionnaire. After implementing propensity score matching (PSM) using factors that affect the QoL of DN patients, QoL differences between DN and non-DN participants were examined. RESULTS: Among all DN patients (n = 390), higher QoL scores were found for taller subjects, and lower scores were found for those who were unemployed or unmarried, received Medical Aid, had lower economic status, had higher platelet counts or alkaline phosphatase levels, or used clopidogrel or insulin. After PSM, the 239 matched DN subjects reported significantly lower patient satisfaction (59.9 vs. 64.5, p = 0.02) and general health (35.3 vs. 39.1, p = 0.04) than the 239 non-DN subjects. Scores decreased in both groups during the 5-year follow-up, and the scores in the work status, sexual function, and role-physical domains were lower among DN patients than non-DN patients, though those differences were not statistically significant. CONCLUSION: Socioeconomic factors of DN were strong risk factors for impaired QoL, as were high platelet, alkaline phosphatase, and clopidogrel and insulin use. Clinicians should keep in mind that the QoL of DN patients might decrease in some domains compared with non-DN CKDs.

Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: Results from the KNOW-CKD.

BACKGROUND AND AIMS: The optimal low-density lipoprotein cholesterol (LDL-C) level to prevent cardiovascular disease in chronic kidney disease (CKD) patients remains unknown. This study aimed to explore the association of LDL-C levels with adverse cardiovascular and kidney outcomes in Korean CKD patients and determine the validity of "the lower, the better" strategy for statin intake. METHODS AND RESULTS: A total of 1886 patients from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) were included. Patients were classified into four LDL-C categories: <70, 70-99, 100-129, and ≥130 mg/dL. The primary outcome was extended major adverse cardiovascular events (eMACEs). Secondary outcomes included all-cause mortality, and CKD progression. During the follow-up period, the primary outcome events occurred in 136 (7.2%) patients (16.9 per 1000 person-years). There was a graded association between LDL-C and the risk of eMACEs. The hazard ratios (95% confidence intervals) for LDL-C categories of 70-99, 100-129, and ≥130 mg/dL were 2.06 (1.14-3.73), 2.79 (1.18-6.58), and 4.10 (1.17-14.3), respectively, compared to LDL-C <70 mg/dL. Time-varying analysis showed consistent findings. The predictive performance of LDL-C for eMACEs was affected by kidney function. Higher LDL-C levels were also associated with significantly higher risks of CKD progression. However, LDL-C level was not associated with all-cause mortality. CONCLUSIONS: This study showed a graded relationship between LDL-C and the risk of adverse cardiovascular outcome in CKD patients. The lowest risk was observed with LDL-C <70 mg/dL, suggesting that a lower LDL-C target may be acceptable.

Effects of blood urea nitrogen independent of the estimated glomerular filtration rate on the development of anemia in non-dialysis chronic kidney disease: The results of the KNOW-CKD study.

BACKGROUND: Anemia is a common complication of chronic kidney disease (CKD). Blood urea nitrogen (BUN) in CKD represents nitrogenous uremic toxin accumulation which could be involved in anemia of CKD. We investigated the effects of BUN independent of estimated glomerular filtration rate (eGFR) on anemia in non-dialysis CKD (NDCKD). METHODS: This prospective study included 2,196 subjects enrolled in the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort with BUN and hemoglobin level data. Initially, we investigated the association between BUN and hemoglobin level. To examine the impact of baseline BUN on the incident anemia, a longitudinal study was performed on 1,169 patients without anemia at study enrollment. BUN residuals were obtained from the fitted curve between BUN and eGFR. Anemia was defined as a hemoglobin level of <13.0 g/dL for men and <12.0 g/dL for women. RESULTS: BUN residuals were not related to eGFR but to daily protein intake (DPI), while BUN was related to both eGFR and DPI. BUN was inversely associated with hemoglobin level (ß -0.03; 95% confidence interval [CI] -0.04, -0.03; P <0.001) in the multivariable linear regression analysis adjusted for multiple confounders including eGFR, and BUN residual used instead of BUN was also inversely associated with hemoglobin level (ß -0.03; 95% CI -0.04, -0.02; P <0.001). Among the 1,169 subjects without anemia at baseline, 414 (35.4%) subjects newly developed anemia during the follow-up period of 37.5 ± 22.1 months. In the multivariable Cox regression analysis with adjustment, both high BUN level (Hazard ratio [HR] 1.02; 95% CI 1.01, 1.04; P = 0.002) and BUN residual used instead of BUN (HR 1.02; 95% CI 1.00, 1.04; P = 0.031) increased the risk of anemia development. Moreover, BUN, rather than eGFR, increased the risk of anemia development in patients with CKD stage 3 in the multivariable Cox regression. CONCLUSION: Higher BUN levels derived from inappropriately high protein intake relative to renal function were associated with low hemoglobin levels and the increased risk of anemia independent of eGFR in NDCKD patients.

Persistent Resistant Hypertension Has Worse Renal Outcomes in Chronic Kidney Disease than that Resolved in Two Years: Results from the KNOW-CKD Study.

Apparent treatment-resistant hypertension (ATRH) is closely related to chronic kidney disease (CKD); however, the long-term outcomes and the effects of improvement in ATRH in patients with CKD are not well understood. We evaluated the relationship between the persistence of ATRH and the progression of CKD. This cohort study enrolled 1921 patients with CKD. ATRH was defined as blood pressure above 140/90 mmHg and intake of three different types of antihypertensive agents, including diuretics, or intake of four or more different types of antihypertensive agents, regardless of blood pressure. We defined ATRH subgroups according to the ATRH status at the index year and two years later. The prevalence of ATRH at baseline was 14.0%. The presence of ATRH at both time points was an independent risk factor for end-point renal outcome (HR, 1.41; 95% CI, 1.04-1.92; p = 0.027). On the other hand, the presence of ATRH at any one of the time points was not statistically significant. In conclusion, persistent ATRH is more important for the prognosis of renal disease than the initial ATRH status. Continuous follow-up and appropriate treatment are important to improve the renal outcomes.

Metabolic Acidosis Is an Independent Risk Factor of Renal Progression in Korean Chronic Kidney Disease Patients: The KNOW-CKD Study Results.

Background: We aimed to evaluate serum bicarbonate as a risk factor for renal progression, cardiovascular events, and mortality in Korean CKD patients. Methods: We analyzed 1,808 participants from a Korean CKD cohort whose serum bicarbonate levels were measured at enrollment. Serum bicarbonate levels were categorized as low, lower normal, higher normal, and high (total carbon dioxide <22, 22-26, 26.1-29.9, and ≥30 mmol/L, respectively) groups. Metabolic acidosis was defined as a serum bicarbonate level <22 mmol/L. The primary outcome was renal events defined as doubling of serum creatinine, 50% reduction of eGFR from the baseline values, or development of end-stage kidney disease. The secondary outcome consisted of cardiovascular events and death. In addition, patients whose eGFR values were measured more than three times during the follow-up period were analyzed for eGFR decline. The rapid decline in eGFR was defined as lower than the median value of the eGFR slope. Results: The mean serum bicarbonate level was 25.7 ± 3.7 mmol/L and 240 (13.2%) patients had metabolic acidosis. During the follow-up period of 55.2 ± 24.1 months, 545 (30.9%) patients developed renal events and 187 (10.6%) patients developed a composite of cardiovascular events and death. After adjustment, the low serum bicarbonate group experienced 1.27 times more renal events than the lower normal bicarbonate group [hazard ratio (HR): 1.27; 95% CI: 1.01-1.60, P = 0.043]. There was no significant association between the bicarbonate groups and the composite outcome of cardiovascular events and death. The low bicarbonate group showed a significantly rapid decline in eGFR [odds ratio (OR): 2.12; 95% CI: 1.39-3.22, P < 0.001] compared to the lower normal bicarbonate group. Conclusions: Metabolic acidosis was significantly associated with increased renal events and a rapid decline in renal function in Korean predialysis CKD patients.

Association of Blood Pressure With the Progression of CKD: Findings From KNOW-CKD Study.

RATIONALE & OBJECTIVE: Optimal blood pressure (BP) control is a major therapeutic strategy in the management of chronic kidney disease (CKD). We studied the association between BP and adverse kidney outcomes within a diverse cohort of Koreans with CKD. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 2,044 participants from the Korean Cohort Study for Outcomes in Patients With CKD (KNOW-CKD). EXPOSURES: Baseline and time-updated systolic BP (SBP) and diastolic BP (DBP). OUTCOME: A composite kidney outcome of a≥50% decline in estimated glomerular filtration rate (eGFR) from the baseline value or incident kidney replacement therapy. ANALYTICAL APPROACH: Multivariate cause-specific hazards models and marginal structural models were fitted for baseline and time-updated BP, respectively. RESULTS: During 7,472 person-years of follow-up, the primary composite kidney outcome occurred in 473 participants (23.1%), an incidence rate of 63.3 per 1,000 patient-years. Compared with baseline SBP<120mm Hg, the hazard ratios (HRs) for 120-129, 130-139, and≥140mm Hg were 1.10 (95% CI, 0.83-1.44), 1.20 (95% CI, 0.93-1.59), and 1.43 (95% CI, 1.07-1.91), respectively. This association was more evident in the model with time-updated SBP, for which the corresponding HRs were 1.31 (95% CI, 0.98-1.75), 1.59 (95% CI, 1.16-2.16), and 2.29 (95% CI, 1.69-3.11), respectively. In the analyses of DBP, we observed that time-updated DBP but not baseline DBP was significantly associated with the composite kidney outcome. Compared to patients with SBP<120mm Hg, patients with higher SBP had steeper slopes of eGFR decline. In the model including both SBP and DBP, only SBP was significantly associated with the composite kidney outcome. LIMITATIONS: Observational design, unmeasured confounders, and use of office BPs only. CONCLUSIONS: In patients with CKD, higher SBP and DBP levels were associated with a higher risk of a composite kidney outcome reflecting CKD progression. SBP had a greater association with adverse kidney outcomes than DBP.

Urinary chloride concentration and progression of chronic kidney disease: results from the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease.

BACKGROUND: Urinary chloride is regulated by kidney transport channels, and high urinary chloride concentration in the distal tubules can trigger tubuloglomerular feedback. However, little attention has been paid to urinary chloride as a biomarker of clinical outcomes. Here, we studied the relationship between urinary chloride concentration and chronic kidney disease (CKD) progression. METHODS: We included 2086 participants with CKD from the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease. Patients were categorized into three groups, according to baseline urinary chloride concentration tertiles. The study endpoint was a composite of ≥50% decrease in estimated glomerular filtration rate from baseline values, or end-stage kidney disease. RESULTS: During a median follow-up period of 3.4 years (7452 person-years), 565 participants reached the primary endpoint. There was a higher rate of CKD progression events in the lowest and middle tertiles than in the highest tertile. Compared with the lowest tertile, the highest tertile was associated with 33% [95% confidence interval (CI) 0.49-0.90] lower risk for the primary outcome in a cause-specific hazard model after adjustment for confounding variables. In addition, for every 25 mEq/L increase in urinary chloride concentration, there was 11% (95% CI 0.83-0.96) lower risk for CKD progression. This association was consistent in a time-varying model. Urinary chloride concentration correlated well with tubule function and kidney injury markers, and its predictive performance for CKD progression was comparable to that of these markers. CONCLUSIONS: In this hypothesis-generating study, low urinary chloride concentration was associated with a higher risk for CKD progression.

Association of Body Weight Variability With Progression of Coronary Artery Calcification in Patients With Predialysis Chronic Kidney Disease.

BACKGROUND: We investigated whether high body weight variability (BWV) is associated with a higher prevalence of coronary artery calcification (CAC) or more rapid progression of CAC in patients with predialysis chronic kidney disease (CKD). METHODS: A total of 1,162 subjects from a nationwide prospective cohort of predialysis CKD were analyzed. The subjects were divided into the tertile (T1, T2, and T3) by BWV. CAC was assessed at the baseline and a 4-year follow-up by CT scan. Rapid progression of coronary artery calcification was defined as an increase in coronary artery calcium score (CACS) more than 200 Agatston units during a 4-year follow-up. RESULTS: One-way ANOVA revealed that CACS change during the follow-up period is significantly higher in the subjects with high BWV, although CACS at the baseline and 4-year follow-up was not different among the tertile groups by BWV. Logistic regression analysis revealed that compared to low BWV (T1), both moderate (T2, adjusted odds ratio (OR) 2.118, 95% CI 1.075-4.175) and high (T3, adjusted OR 2.602, 95% CI 1.304-5.191) BWV was associated with significantly increased risk of rapid progression of CAC. Importantly, the association between BWV and progression of CAC remained robust even among the subjects without significant BW gain or loss during follow-up periods (T2, adjusted OR 2.007, 95% CI 1.011-3.984; T3, adjusted OR 2.054, 95% CI 1.003-4.207). CONCLUSION: High BWV is independently associated with rapid progression of CAC in patients with predialysis CKD.

Effect of ambulatory blood pressure monitoring guided antihypertensive treatment on renal progression in patients with chronic kidney disease: a randomized comparative study.

OBJECTIVES: Adequate blood pressure (BP) control is pivotal for managing chronic kidney disease (CKD). The optimal approach for monitoring BP to delay CKD progression is not yet clear. METHODS: Patients with hypertension and CKD stage 3-4 were randomized into ambulatory blood pressure monitoring (ABPM) or office BP groups. All patients had ABPM at baseline and 18 months, and the ABPM group additionally underwent ABPM at 3 and 6 months. Each ABPM result was notified only for the ABPM group. The BP target was daytime ABP less than 135/85 mmHg for the ABPM group and office BP less than 140/90 mmHg for the office BP group. The primary outcome was decrease in estimated glomerular filtration rate (eGFR) during 18 months. RESULTS: A total of 146 patients were randomized into the ABPM (n = 69) and office BP groups (n = 77). Although office BP was comparable in the two groups at baseline, daytime ABP was higher in the ABPM group (median 140 vs. 132 mmHg). Initial eGFR was 35.7 ±â€Š12.5 ml/min per 1.73 m2 in the ABPM group and 34.6 ±â€Š12.0 ml/min per 1.73 m2 in the office BP group. eGFR change was -5.5 [95% confidence interval (95% CI) -7.7 to  -3.4] ml/min per 1.73 m2 in the ABPM group and -5.0 (95% CI -6.9 to -3.0) ml/min per 1.73 m2 in the office BP group (P = 0.704). Renal events occurred in 10 patients (15.6%) from the ABPM group and five (7.1%) from the office BP group (P = 0.120). CONCLUSION: The present study did not show a beneficial effect of ABPM for controlling hypertension in CKD compared with conventional office BP monitoring in terms of renal outcomes.

Effect of urinary angiotensinogen and high-salt diet on blood pressure in patients with chronic kidney disease: results from the Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease (KNOW-CKD).

BACKGROUND/AIMS: This study aimed to investigate whether urinary angiotensinogen (UAGT) excretion was associated with elevated blood pressure in patients with chronic kidney disease (CKD) and to evaluate the relationship among blood pressure, intra-renal renin-angiotensin system (RAS) activity, and dietary sodium in patients with CKD. METHODS: Participants from the Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease (KNOW-CKD) were included. Of the total cohort of 2,238 individuals with CKD, we included 1,955 participants who underwent complete 24-hour urinary sodium (24-hour UNa) analysis. They were categorized into three groups according to three tertiles of their 24-hour UNa, reflecting daily salt intake. To measure intra-renal RAS activity, the UAGT excretion was assayed with an enzyme-linked immunosorbent assay. RESULTS: Elevated 24-hour UNa levels, logarithm of UAGT-to-creatinine ratio (UAGT/Cr), increased waist-to-hip ratio, and decreased estimated glomerular filtration rate were the risk factors for increased systolic blood pressure. Systolic blood pressure showed a positive correlation with 24-hour UNa levels and logarithm of UAGT/Cr. CONCLUSION: UAGT and urinary sodium excretion are independent determinants of systolic blood pressure in patients with CKD. These findings suggest that increased systolic blood pressure in CKD patients is associated with both increased dietary sodium levels and intra-renal RAS activity. The risk of elevated systolic blood pressure in the 3rd tertile of both the UAGT/Cr and 24-hour UNa groups was about 2.3 times higher than that in the reference group.