KoreaN Cohort Study For Outcomes In Patients With Chronic Kidney Disease Research Articles

#210 Effects of serum magnesium level on kidney disease progression and major cardiovascular outcome in patients with chronic kidney disease

Abstract Background and Aims Magnesium is known for its anti-inflammatory, anti-apoptotic, and anti-oxidative effects, potentially inhibiting renal fibrosis. Additionally, it is believed that magnesium can inhibit vascular calcification, potentially improving cardiovascular outcomes. However, this remains a topic of controversy. This study aims to investigate the association between serum magnesium levels and CKD progression as well as cardiovascular outcomes. Method We analyzed 1,893 patients from The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD), which is a prospective cohort study. These patients were categorized into three groups based on their baseline magnesium levels: Mg1 (hypomagnesemia, <1.8 mg/dL), Mg2 (normomagnesemia, 1.8-2.4 mg/dL), and Mg3 (hypermagnesemia, >2.4 mg/dL). The primary outcome was defined as meeting one or more of the following criteria during the follow-up period: initiation of dialysis or transplantation, a two-fold increase in baseline serum creatinine levels, or a 50% decline in the estimated glomerular filtration rate. The secondary outcome was a composite of major adverse cardiovascular events (MACEs). We used Cox proportional hazard regression model. Results A total of 673 patients (35.6%) experienced the composite renal outcome. The Mg1 group showed significantly increased adverse renal outcomes compared to the Mg2 group (HR, 1.885; 95% CI, 1.137-3.124; p = 0.013), however, Mg3 group did not show a significant difference (HR, 0.927; 95% CI, 0.783-1.097; p = 0.379). The composite cardiovascular outcome occurred in 138 patients (7.3%). The risk of composite cardiovascular outcomes significantly increased in the Mg1 group compared to the Mg2 group (HR 3.472; 95% CI, 1.492-8.076; p = 0.003). However, we observed no statistically significant differences in the Mg3 group (HR 1.021; 95% CI, 0.689; p = 0.913). The cubic spline curves demonstrated a U-shaped association between serum magnesium levels and both renal and cardiovascular outcomes. Conclusion Hypomagnesemia is associated with the progression of renal disease and a significant increase in MACEs. Beyond a certain level, hypermagnesemia may also be associated with worsening renal and cardiovascular outcomes.

Association between progression of coronary artery calcification and development of kidney failure with replacement therapy: Findings from KNOW-CKD study

Background and aimsHigh 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). MethodsWe 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. ResultsDuring 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. ConclusionsCAC 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.

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

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. 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 KNOW-CKD (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. 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. 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.

Systolic blood pressure, low-density lipoprotein cholesterol levels, and adverse kidney outcome: results from KNOW-CKD.

It is unknown whether intensive control of blood pressure (BP) and lipids can delay the progression of chronic kidney disease (CKD). This study examined the combined association of strict targets of systolic BP (SBP) and low-density lipoprotein cholesterol (LDL-C) levels with adverse kidney outcomes. In total, 2012 patients from the KoreaN Cohort Study for Outcomes in Patients With CKD (KNOW-CKD) were classified into four groups according to SBP of 120 mmHg and LDL-C of 70 mg/dl: group 1, <120 and <70; group 2, <120 and ≥70; group 3, ≥120 and <70; group 4, ≥120 and ≥70. We constructed time-varying models treating two variables as time-varying exposures. The primary outcome was the progression of CKD, defined as a ≥50% decrease in estimated glomerular filtration rate from the baseline or the onset of kidney failure requiring replacement therapy. The primary outcome events occurred in 27.9%, 26.7%, 40.3%, and 39.1% from groups 1 to 4. In the time-varying model, the hazard ratios (95% confidence intervals) for the primary outcome were 0.48 (0.33-0.69), 0.78 (0.63-0.96), and 0.96 (0.74-1.23) for groups 1 to 3, respectively, compared with group 4. When less stringent cut-offs of SBP of 130 mmHg and LDL-C of 100 mg/dl were used, this graded association was lost, while only SBP was associated with adverse kidney outcomes. In this study, the lower targets of SBP of <120 mmHg and LDL-C < 70 mg/dl were synergistically associated with a lower risk of adverse kidney outcomes.

The association between vitamin D deficiency and risk of renal event: Results from the Korean cohort study for outcomes in patients with chronic kidney disease (KNOW-CKD).

Some observational studies have suggested a possible association between vitamin D deficiency and CKD. However, in most studies, the causality between low levels of vitamin D and risk of renal events could not be explained. We investigated the relationship between vitamin D deficiency and risk of severe CKD stage and renal event in a large-scale prospective cohort study. We used data from a prospective cohort of 2,144 patients with available information on serum 25-hydroxyvitamin D (25(OH)D) levels at baseline from KNOW-CKD, 2011-2015 were included. Vitamin D deficiency was defined as serum 25(OH)D levels < 15 ng/mL. We performed a cross-sectional analysis to elucidate the relationship between 25(OH)D and CKD stage using baseline CKD patient data. We further examined a cohort analysis to clarify the association between 25(OH)D and risk of renal event. Renal event was a composite of the first occurrence of a 50% decline in eGFR from the baseline value or the onset of CKD stage 5 (initiation of dialysis or kidney transplantation) across the follow-up period. We also investigated the associations of vitamin D deficiency with risk of renal event according to diabetes and overweight status. Vitamin D deficiency were significantly associated with an increased risk of severe CKD stage - 1.30-fold (95% CI: 1.10-1.69) for 25(OH)D. Deficiency of 25(OH)D with 1.64-fold (95% CI: 1.32-2.65) was related to renal event compared with the reference. Furthermore, vitamin D deficiency patients with presence of DM and overweight status also displayed higher risk than non-deficient patients for risk of renal event. Vitamin D deficiency is associated with significantly increased risk of severe CKD stage and renal event.

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.

Urinary Angiotensinogen and Progression of Chronic Kidney Disease: Results from KNOW-CKD Study

The prognostic value of urinary angiotensinogen (UAGT) in patients with chronic kidney disease (CKD) has not been completely evaluated, although the association of UAGT with renal outcomes has been suggested in specific subsets of CKD. In the present study, to investigate the association of UAGT with renal outcomes in patients with non-dialysis CKD irrespective of the primary cause, a total of 1688 subjects from the Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) were prospectively analyzed. The subjects were divided into the quintile by UAGT to urine creatinine ratio (UAGT/Cr) level. The primary outcomes of interest were composite renal event, which included decline in kidney function and onset of end-stage renal disease during follow-up periods. The median follow-up duration was 6.257 years. Cox regression model analysis unveiled that the risk of composite renal event was significantly higher in the fifth quintile (adjusted hazard ratio 1.528, 95% confidence interval 1.156 to 2.021) compared to that of the first quartile. The association between high UAGT/Cr level and adverse renal outcome remained consistent in sensitivity analyses, including the analysis of the cause-specific hazard model. Subgroup analyses revealed that the association of UAGT level with renal outcomes is modified by certain clinical contexts, such as BMI and albuminuria. In conclusion, high UAGT level is associated with adverse renal outcomes in patients with non-dialysis CKD. Further studies are warranted to elaborate and expand the predictive role of UAGT as a biomarker for renal outcomes in CKD.

The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD): A Korean Chronic Kidney Disease Cohort

The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was launched in 2011 with the support of the Korea Disease Control and Prevention Agency. The study was designed with the aim of exploring the various clinical features and characteristics of chronic kidney disease (CKD) in Koreans, and elucidating the risk factors for CKD progression and adverse outcomes of CKD. For the cohort study, nephrologists at 9 tertiary university-affiliated hospitals participated in patient recruitment and follow-up. Biostatisticians and epidemiologists also participated in the basic design and structuring of the study. From 2011 until 2016, the KNOW-CKD Phase I recruited 2238 adult patients with CKD from stages G1 to G5, who were not receiving renal replacement therapy. The KNOW-CKD Phase II recruitment was started in 2019, with an enrollment target of 1500 subjects, focused on diabetic nephropathy and hypertensive kidney diseases in patients with reduced kidney function who are presumed to be at a higher risk of adverse outcomes. As of 2021, the KNOW-CKD investigators have published articles in the fields of socioeconomics, quality of life, nutrition, physical activity, renal progression, cardiovascular disease and outcomes, anemia, mineral bone disease, serum and urine biomarkers, and international and inter-ethnic comparisons. The KNOW-CKD researchers will elaborate a prediction model for various outcomes of CKD such as the development of end-stage kidney disease, major adverse cardiovascular events, and death.

Association of Left Ventricular Diastolic Dysfunction With Cardiovascular Outcomes in Patients With Pre-dialysis Chronic Kidney Disease: Findings From KNOW-CKD Study.

BackgroundThe impact of left ventricular diastolic dysfunction (LVDD) on cardiovascular (CV) outcomes in patients with pre-dialysis chronic kidney disease (CKD) has been rarely unveiled. We here investigated the association of LVDD with CV outcomes and all-cause mortality in patients with pre-dialysis CKD.MethodsA total of 2,135 patients with pre-dialysis CKD from the Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) cohort were dichotomized by the absence or presence of LVDD, which was defined as the ratio of the early transmitral blood flow velocity to early diastolic velocity of the mitral annulus (E/e′) > 14.ResultsCox regression analysis revealed that LVDD was significantly associated with increased risk of composite CV events [adjusted hazard ratio (HR) 2.194, 95% confidence interval (CI) 1.486–3.240] and all-cause mortality (adjusted HR 1.830, 95% CI 1.168–2.869). Restricted cubic splines visualized stringent linear correlations of E/e′ with both composite CV events and all-cause mortality. In the sensitivity analysis only including the subjects with left ventricular ejection fraction ≥ 50%, LVDD was still significantly associated with adverse CV outcomes (adjusted HR 1.984, 95% CI 1.325–3.000) and all-cause mortality (adjusted HR 1.727, 95% CI 1.083–2.754), suggesting that the impact of LVDD on the outcomes in patients with CKD is independent of LV systolic function. Subgroup analyses revealed that the associations were not modified by various clinical contexts, such as age, sex, burden of comorbid conditions, body mass index, estimated glomerular filtration rate, and albuminuria.ConclusionLVDD is independently associated with adverse CV outcomes and all-cause mortality in patients with pre-dialysis CKD.

Predictive Model for High Coronary Artery Calcium Score in Young Patients with Non-Dialysis Chronic Kidney Disease.

Cardiovascular disease is a major complication of chronic kidney disease. The coronary artery calcium (CAC) score is a surrogate marker for the risk of coronary artery disease. The purpose of this study is to predict outcomes for non-dialysis chronic kidney disease patients under the age of 60 with high CAC scores using machine learning techniques. We developed the predictive models with a chronic kidney disease representative cohort, the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD). We divided the cohort into a training dataset (70%) and a validation dataset (30%). The test dataset incorporated an external dataset of patients that were not included in the KNOW-CKD cohort. Support vector machine, random forest, XGboost, logistic regression, and multi-perceptron neural network models were used in the predictive models. We evaluated the model’s performance using the area under the receiver operating characteristic (AUROC) curve. Shapley additive explanation values were applied to select the important features. The random forest model showed the best predictive performance (AUROC 0.87) and there was a statistically significant difference between the traditional logistic regression model and the test dataset. This study will help identify patients at high risk of cardiovascular complications in young chronic kidney disease and establish individualized treatment strategies.

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.

BackgroundDiabetic 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).MethodsThe 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.ResultsAmong 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.ConclusionSocioeconomic 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.

Association of Body Weight Variability with Adverse Cardiovascular Outcomes in Patients with Pre-Dialysis Chronic Kidney Disease.

To investigate the association of body weight variability (BWV) with adverse cardiovascular (CV) outcomes in patient with pre-dialysis chronic kidney disease (CKD), a total of 1867 participants with pre-dialysis CKD from Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) were analyzed. BWV was defined as the average absolute difference between successive values. The primary outcome was a composite of non-fatal CV events and all-cause mortality. Secondary outcomes were fatal and non-fatal CV events and all-cause mortality. High BWV was associated with increased risk of the composite outcome (adjusted hazard ratio (HR) 1.745, 95% confidence interval (CI) 1.065 to 2.847) as well as fatal and non-fatal CV events (adjusted HR 1.845, 95% CI 1.136 to 2.996) and all-cause mortality (adjusted HR 1.861, 95% CI 1.101 to 3.145). High BWV was associated with increased risk of fatal and non-fatal CV events, even in subjects without significant body weight gain or loss during follow-up periods (adjusted HR 2.755, 95% CI 1.114 to 6.813). In conclusion, high BWV is associated with adverse CV outcomes in patients with pre-dialysis CKD.

Association Between Longitudinal Blood Pressure Trajectory and the Progression of Chronic Kidney Disease: Results From the KNOW-CKD.

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

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. Prospective observational cohort study. 2,044 participants from the Korean Cohort Study for Outcomes in Patients With CKD (KNOW-CKD). Baseline and time-updated systolic BP (SBP) and diastolic BP (DBP). A composite kidney outcome of a≥50% decline in estimated glomerular filtration rate (eGFR) from the baseline value or incident kidney replacement therapy. Multivariate cause-specific hazards models and marginal structural models were fitted for baseline and time-updated BP, respectively. 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. Observational design, unmeasured confounders, and use of office BPs only. 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.

The KNOW-CKD Study: What we have learned about chronic kidney diseases.

As the nation’s largest chronic kidney disease (CKD) cohort, the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was established to investigate the clinical course, risk factors for progression, and adverse outcomes of CKD. From 2011 to 2016, the KNOW-CKD recruited 2,238 adult patients with CKD from stage G1 to G5 who were not receiving renal replacement therapy from nine tertiary care hospitals throughout Korea. As of 2019, the KNOW-CKD has published more than 50 articles in the areas of socio-economics, nutrition, quality of life, health-related habits, CKD progression, cardiovascular comorbidity and outcome, anemia, mineral bone disease, biomarker discovery, and international and inter-ethnic comparisons. The KNOW-CKD will eventually offer a prediction model for long-term consequences of CKD, such as the occurrences of end-stage renal disease, cardiovascular disease, and death, thereby enabling the identification and treatment of at-risk populations that require extra medical attention.

Urinary Angiotensinogen in addition to Imaging Classification in the Prediction of Renal Outcome in Autosomal Dominant Polycystic Kidney Disease.

BackgroundIntrarenal renin-angiotensin system (RAS) is known to play the major role in the development of hypertension and renal progression in autosomal dominant polycystic kidney disease (ADPKD). Urinary angiotensinogen to creatinine ratio (AGT/Cr) was suggested as a novel biomarker to reflect intrarenal RAS activity. This study was performed to evaluate urinary AGT/Cr as a predictive biomarker for renal function decline in addition to imaging classification in a prospective ADPKD cohort.MethodsFrom 2011 to 2016, a total of 364 ADPKD patients were enrolled in the prospective cohort called the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Among them, a total of 207 subjects in chronic kidney disease stage 1–4 with baseline urinary AGT and total kidney volume and subsequent renal function follow-up data over more than 1 year were included in the analysis. Patients were defined as slow progressors (SP) if they are classified as 1A or 1B by imaging classification whereas rapid progressors (RP) if they are classified as 1C–1E. Patients were divided according to AGT/Cr quartiles and annual estimated glomerular filtration rate (eGFR) slope was compared among highest quartile (hAGT group) and the rest of quartiles (lAGT group). Patients were divided into 4 groups to evaluate the predictive value of urinary AGT/Cr in addition to imaging classification: SP/lAGT, SP/hAGT, RP/lAGT, and RP/hAGT. The Cox regression model was used to evaluate the hazard ratio (HR) between groups.ResultsThe mean age was 45.9 years and 88.9% had hypertension. Baseline eGFR was 79.0 ± 28.4 mL/min/1.73 m2 and median height-adjusted total kidney volume was 788.2 (471.2; 1,205.2) mL/m. The patients in the hAGT group showed lower eGFR (72.4 ± 24.8 vs. 81.1 ± 29.2 mL/min/1.73 m2, P = 0.039), lower plasma hemoglobin (13.0 ± 1.4 vs. 13.7 ± 1.6 g/dL, P = 0.007), higher urinary protein to creatinine ratio (0.14 [0.09, 0.38] vs. 0.07 [0.04, 0.12] g/g, P = 0.007) compared to the lAGT group. The hAGT group was an independent risk factor for faster eGFR decline after adjusting for gender, RP, baseline eGFR, and other known risk factors. During median follow-up duration of 4.6 years, a total of 29 renal events (14.0%) occurred. The SP/hAGT group showed significantly higher risk of developing renal outcome compared to SP/lAGT group (HR, 13.4; 95% confidence interval, 1.282–139.324; P = 0.03).ConclusionUrinary AGT/Cr can be a useful predictive marker in the patients with relatively small ADPKD. Various biomarkers should be considered to define RP when implementing novel treatment in the patients with ADPKD.

SUN-199 URINARY ANGIOTENSINOGEN TO CREATININE RATIO (UAGT/CR) IS NOT A PREDICTIVE BIOMARKER FOR RENAL PROGRESSION IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: KNOW-CKD STUDY

Decreased renal blood flow by cystic compression and subsequent hypertension has been suggested as one of the main mechanisms for renal progression in autosomal dominant polycystic kidney disease (ADPKD) and intrarenal renin-angiotensin-aldosterone system (RAAS) is known to play the major role in this process. Urinary angiotensinogen to creatinine ratio (UAGT/Cr) was suggested as a novel biomarker to reflect intrarenal RAAS activity. Previous study demonstrated that ADPKD patients have 5- to 6- fold higher level of UAGT/Cr compared to non-ADPKD CKD patients and the level of UAGT/Cr was associated with decreased renal function. However, whether UAGT/Cr can predict renal function decline or kidney growth has not been elucidated. This study was performed to evaluate UAGT/Cr in a prospective ADPKD cohort and demonstrate its usefulness as a predictive biomarker in ADPKD patients. From April 2011 to February 2016, a total of 364 ADPKD patients were enrolled in the prospective cohort called KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). UAGT was measured by commercial sandwich enzyme-linked immunosorbent assay (ELISA) (Immuno-Biological Laboratories, Co., Ltd., Gunma, Japan) and adjusted by urinary creatinine (Cr) content. Serum Cr was measured by IDMS-traceable method at a central laboratory and glomerular filtration rate (GFR) was estimated by CKD-EPI(Cr) equation. Annual GFR decline rate was calculated from the difference between final and initial Cr divided by follow-up years. Total kidney volume (TKV) was measured upon enrollment and every two years afterwards. HtTKV was calculated by TKV divided by the height of the patient. The annual eGFR decline rate and HtTKV growth rate was compared among UAGT/Cr quartile groups. The variables that do not follow normal distribution was natural log-transformed before analysis. The mean age was 47 years and male were 184 (50.5%). Most of the patients were taking angiotensin converting enzyme inhibitors or angiotensin receptor blockers (85.9%). Baseline estimated GFR was 68.1±33.3 mL/min/1.73m2 and HtTKV was 740.7±541.6 cc/m. Mean UAGT.Cr was 16.3±45.3 μg/g. Ln(UAGT/Cr) was negatively correlated with estimated GFR (r2=0.03, p=0.001) and positively correlated with Ln(HtTKV) (r2=0.03, p=0.004). UAGT/Cr was significantly increased as CKD stage progressed (8.1±20.9 in stage 1 vs. 8.9±16.4 in stage 2 vs. 12.9±16.2 in stage 3 vs. 28.6±74.1 in stage 4 vs. 125.2±138.4 in stage 5, p<0.001). A total of 246 patients with relatively preserved GFR (>30 mL/min/1.73m2) were evaluated for the effect of UAGT/Cr upon prospective eGFR decline rate and HtTKV growth rate. The mean follow-up duration was 45.3±14.8 months. The highest quartile UAGT/Cr group showed higher systolic and diastolic blood pressure (131.9±13.6 and 83.0±10.9 mmHg, p<0.05), lower GFR at baseline (63.9±20.9 mL/min/1.73m2, p<0.001) and higher HtTKV (816.5±499.2 cc/m, p=0.079). However, neither annual GFR decline rate or HtTKV growth rate was statistically different among UAGT/Cr quartile groups. Ln(UAGT/Cr) was not associated with either annual GFR decline rate (r2=0.01, p=0.876) or Ln(HtTKV growth rate) (r2=0.036, p=0.761). UAGT/Cr is a marker of concurrent renal function and HtTKV. However, UAGT/Cr cannot predict renal progression in ADPKD.

Hyperuricemia has increased the risk of progression of chronic kidney disease: propensity score matching analysis from the KNOW-CKD study

The prevalence of hyperuricemia and chronic kidney disease (CKD) has been steadily increasing. The role of hyperuricemia and efficacy of uric acid-lowering agents against CKD progression remain controversial. This study aimed to evaluate the effect of hyperuricemia and uric acid-lowering agents on the progression of CKD. A total 2042 patients with CKD were analyzed in the KoreaN cohort Study for Outcomes in patients With Chronic Kidney Disease (KNOW-CKD), a prospective cohort study. Patients were classified into quartiles on the basis of their serum uric acid level and the prevalence of advanced CKD was higher in patients with a high uric acid level. A composite renal outcome was defined as one or more of the following: initiation of dialysis or transplantation, a two-fold increase in baseline serum creatinine levels, or a 50% decline in the estimated glomerular filtration rate during the follow-up period. A Cox proportional hazard ratio model was applied to analyze the relationship between composite renal outcome and uric acid levels. The risk of progression to renal failure increased by 28% (hazard ratio [HR], 1.277; 95% confidence interval [CI], 1.212–1.345) for each 1 mg/dl increase in the baseline uric acid level. In multivariate models, an association was found between the highest quartile of uric acid and increased risk of composite renal outcome (HR, 3.590; 95% CI, 2.546–5.063). A propensity score matching analysis was performed to survey the effect of uric acid lowering agent. Both allopurinol and febuxostat did not affect the renal outcome. In conclusion, hyperuricemia appears to be an independent risk factor for composite renal outcome, but allopurinol and febuxostat did not show reno-protective effect.

The ratio of urinary sodium and potassium and chronic kidney disease progression: Results from the KoreaN Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD).

The Na/K ratio in urine stands for the dietary of sodium and potassium intake in patients with chronic kidney disease remains unclear for the renal progression. We aimed to determine the risk of progression of chronic kidney disease based on the Na/K ratio in a 24-hour urine collection.We determined the association between the progression of renal disease and 24-hour urinary sodium and potassium (Na/K) ratios in 2238 patients over a 5-year timespan using data obtained from the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease (KNOW-CKD). Renal events were defined as a 50% decrease in the glomerular filtration rate (GFR) below baseline, or the onset of end-stage renal disease (ESRD). Patients were divided into 4 groups based on the quartile range of the 24-hour urinary sodium and potassium ratio. We analyzed those variables in the 4 groups. Multiple logistic regression analyses were performed using the data of 1001 patients to identify the independent factors associated with renal events.Age and male sex accounted for the greatest number of patients in the group with the highest values (group 4) of the 24-hour urinary Na/K ratio (≥3.85). There was no difference in the prevalence of hypertension or diabetes mellitus, the ratio of use of antihypertensive drugs, blood pressures, or estimated GFRs. In the group with the highest urinary Na/K ratio, the 24-hour urinary Na concentration mean ± standard deviation was 188.7 ± 70.6 mmol and that of urinary K was 39.9 ± 16.1 mmol. The urinary protein excretion was highest in the group with the highest urinary Na/K ratio. In the logistic regression analysis, the effect on renal events increased with increasing urinary Na/K ratios. After adjusting for other factors, the risk of renal events was 2.48 (95% confidence interval (CI) 1.30–4.90) in group 3, and 3.75 (95% CI: 1.35–11.27) in group 4. In the Kaplan–Meier analysis, the higher the urinary Na/K ratio, the higher the rate of CKD progression.Based on our analyses, we concluded that the higher the urinary Na/K ratio, the greater the risk of CKD progression.