Moon, Hongran
Lee, Yeonhee
Kim, Sejoong
Kim, Dong Ki
Chin, Ho Jun
Joo, Kwon Wook
Kim, Yon Su
Na, Ki Young
Han, Seung Seok
Background: Obesity is related to several comorbidities and mortality, but its relationship with acute kidney injury (AKI) and long-term mortality remain undetermined in patients undergoing coronary artery bypass grafting.; Methods: Data from 3,018 patients (age =E2=89=A5 18 years) who underwent coronary artery bypass graft surgery from two tertiary referral centers were retrospectively reviewed between 2004 and 2015. Obesity was defined using the body mass index, according to the World Health Organization's recommendation. The odds and hazard ratios in post-surgical, AKI, and all-cause mortality were calculated after adjustment for multiple covariates. Patients were followed for 90 =C2=B1 40.9 months (maximum: 13 years).; Results: Among the cohort, 37.4%, 2.4%, 21.1%, 35.1%, and 4.0% of patients were classified as normal weight, underweight, overweight-at-risk, obese I, and obese II, respectively. Post-surgical AKI developed in 799 patients (26.5%). Patients in the obese groups (overweight-at-risk to obese II) had a higher risk of AKI than did those in the normal-weight group. During the follow-up period, 787 patients (26.1%) died. Underweight patients had a higher risk of mortality than did normal-weight patients, whereas overweight-at-risk, obese I, and obese II patients showed better survival rates.; Conclusion: After coronary artery bypass graft surgery, obese patients encountered a high risk of AKI, and underweight patients exhibited a low chance of survival. Awareness of both obese and underweight statuses should be raised in these patients.=20
Lee, Hajeong
Lee, Jae Wook
Yoo, Kyung Don
Yoo, Joo-Yeon
Lee, Jung Pyo
Kim, Dong Ki
Chin, Ho Jun
Kim, Yon Su
Yang, Seung Hee
T helper 17 (Th17) lymphocytes promote renal inflammation in antiglomerular basement membrane glomerulonephritis (anti-GBM GN), and signal transducer and activator of transcription 3 (STAT3) mediates activation of Th17 lymphocytes by IL-6 and transforming growth factor-beta (TGF-beta). Cln 3-requiring 9 (Ctr9), a subunit of RNA polymerase-associated factor complex (PAFc), regulates the transcription of IL-6/STAT3-dependent genes. Here, we investigated the role of Ctr9 in regulating Th17-driven inflammation in anti-GBM GN. In mice, STAT3 beta or IL-17 knockout ameliorated anti-GBM autoantibody-induced renal injury. This phenomenon was associated with decreases in retinoic acid receptor-related orphan receptor gamma t (ROR gamma t), IL-17, phosphorylated STAT3, and proinflammatory cytokines. Compared with wild-type mice, Ctr9 increased in both STAT3 beta(-/-) and IL-17(-/-) mice injected with anti-GBM IgG, showing a negative correlation with Th17-related transcripts. Small interfering RNA (siRNA)-mediated knockdown of Ctr9 in intrarenal lymphocytes further upregulated Th17-related transcripts, consistent with repression of Th17 differentiation by Ctr9. Interestingly, Ctr9 was also expressed in human and mouse mesangial cells and downregulated in response to anti-GBM IgG or to TGF-beta plus IL-17. Ctr9 in mesangial cells was even more repressed in the presence of both anti-GBM IgG and Th17-activating cytokines. Consistent with these findings, renal biopsies obtained from patients with anti-GBM GN showed consistent downregulation of Ctr9 and upregulation of phosphorylated STAT3 and IL-17 in the glomerulus. We conclude that Ctr9 is a negative regulator of Th17 differentiation in anti-GBM GN and repressed by anti-GBM IgG and IL-17 in mesangial cells.
Xu, Jianwei
Hwang, Sung Il
Lee, Hak Jong
Chin, Ho Jun
Kidney morphology has been used to estimate renal functions. The present study investigated the usefulness of kidney length and renal parenchymal volume (RPV) measured using three-dimensional ultrasonography (3-D USG) in estimating renal pathological findings, and the outcome in patients with nephropathy who underwent renal biopsy. In this study, 94 adult patients who had native kidney biopsy with 3-D USG results were included. The mean kidney length and RPV were independent factors of, and positively correlated to the estimated glomerular filtration rate (eGFR). The mean kidney length and RPV had inverse associations with the percentage of global glomerulosclerosis. Higher mean RPV, other than longer kidney length, indicated a lower prevalence of tubular atrophy. During 63.3 +/- 19.3 months of follow-up, a mean RPV of <125 ml increased the risk of composite outcome by 4.287 fold (95% confidence interval, 1.133-16.227) as compared with a mean RPV of >=3D 125 ml (P=3D0.032). In conclusion, kidney size was inversely associated with certain nephronal damage and positively associated with eGFR in nephropathy. Furthermore, smaller RPVs predicted worse outcomes of nephropathy.
Park, Sehoon
Cho, Hyunjeong
Park, Seokwoo
Lee, Soojin
Kim, Kwangsoo
Yoon, Hyung Jin
Park, Jiwon
Choi, Yunhee
Lee, Suehyun
Kim, Ju Han
Kim, Sejoong
Chin, Ho Jun
Kim, Dong Ki
Joo, Kwon Wook
Kim, Yon Su
Lee, Hajeong
Chin, Ho Jun
Cho, Hyun Jin
Lee, Tae Woo
Na, Ki Young
Yoon, Hyung Jin
Chae, Dong-Wan
Kim, Suhnggwon
Jeon, Un Sil
Do, Jun-Young
Park, Jong-Won
Yoon, Kyung-Woo
Shin, Young-Tai
Lee, Kang Wook
Na, Ki-Ryang
Cha, Dae Ryong
Kang, Young Sun
Han, Seung Seok
Ahn, Shin Young
Ryu, Jiwon
Baek, Seon Ha
Chin, Ho Jun
Na, Ki Young
Chae, Dong-Wan
Kim, Sejoong
BACKGROUND: Proteinuria and hematuria are both important health issues; however, the nature of the association between these findings and acute kidney injury (AKI) or mortality remains unresolved in critically ill patients.; METHODS: Proteinuria and hematuria were measured by a dipstick test and scored using a scale ranging from a negative result to 3+ in 1883 patients admitted to the intensive care unit. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The odds ratios (ORs) for AKI and 3-year mortality were calculated after adjustment for multiple covariates according to the degree of proteinuria or hematuria. For evaluating the synergistic effect on mortality among proteinuria, hematuria, and AKI, the relative excess risk due to interaction (RERI) was used.; RESULTS: Proteinuria and hematuria increased the ORs for AKI: the ORs of proteinuria were 1.66 (+/-), 1.86 (1+), 2.18 (2+), and 4.74 (3+) compared with non-proteinuria; the ORs of hematuria were 1.31 (+/-), 1.58 (1+), 2.63 (2+), and 2.52 (3+) compared with non-hematuria. The correlations between the mortality risk and proteinuria or hematuria were all significant and graded (Ptrend<0.001). There was a relative excess risk of mortality when both AKI and proteinuria or hematuria were considered together: the synergy indexes were 1.30 and 1.23 for proteinuria and hematuria, respectively.; CONCLUSIONS: Proteinuria and hematuria are associated with the risks of AKI and mortality in critically ill patients. Additionally, these findings had a synergistic effect with AKI on mortality.=20
Yu, Mi-Yeon
Kim, Dong Ki
Park, Jung Hwan
Shin, Sung Joon
Lee, Sang Ho
Choi, Bum Soon
Lim, Chun Soo
Chin, Ho Jun
BACKGROUND: Albuminuria is a predictor of disease progression in patients with chronic kidney disease (CKD). However, the ability of proteinuria parameters measured at various time periods to predict renal outcomes is unclear.; METHOD: This observational cohort study included 165 non-diabetic hypertensive CKD patients who took olmesartan medoxomil. We measured the albuminuria at five different time points (0, 2, 4, 26, and 38 months) and the mean levels. The mean albuminuria levels were calculated during 0-4 months, 0-26 months, and 0-38 months. The renal outcome was defined as a decline in eGFR =E2=89=A5 40% during the entire study period.; RESULT: The albuminuria at five different time points and the mean albuminuria levels were independent risk factors for a worse renal outcome after adjusting for age, sex, and estimated glomerular filtration rate (eGFR) at enrollment and were able to predict the renal outcome, although the performance of the estimation tended to be more effective using the mean albuminuria level at the 38-month follow-up time point. The risk of a decline in eGFR =E2=89=A5 40% was increased by 1.690-folds [95% CI 1.110-2.572, P =3D 0.014] per 500 mg/day increase in the mean albuminuria at 38 months. With a cut-off value of 897 mg/day for mean albuminuria at 38 months after treatment, a decline in eGFR =E2=89=A5 40% was predicted with a sensitivity of 88.9% and specificity of 81.3%. The ability of albuminuria to predict a renal event at different measurement points does not differ in CKD patients.; CONCLUSION: The time-averaged albuminuria cut-off of 900 mg/day during the 3-year follow-up period showed high sensitivity and specificity for predicting a decline in eGFR =E2=89=A5 40% in CKD patients, although the albuminuria at different measurement points did not predict a worse renal outcome.=20
Ahn, Shin Young
Kim, Dong Ki
Han, Seung Seok
Park, Jung Hwan
Shin, Sung Joon
Lee, Sang Ho
Choi, Bum Soon
Lim, Chun Soo
Kim, Suhnggwon
Chin, Ho Jun
Background: Weight reduction is a lifestyle intervention that has been introduced for prevention and management of chronic kidney disease (CKD). We investigate the additive anti-proteinuric effect of weight reduction on the usage of angiotensin II receptor blockers (ARBs) and its potential mechanisms in hypertensive CKD patients. Methods: This study is a subanalysis of data from an open-label, randomized, controlled clinical trial. Among the 235 participants, 227 were assigned to subgroups according to changes in body weight. Results: Fifty-eight participants (25.6%) were assigned to group 1 (>=3D 1.5% decrease in body weight after 16 weeks), 32 participants (14.1%) were assigned to group 2 (1.5-0.1% decrease in body weight), and 136 participants (59.9%) were assigned to group 3 (>=3D 0.0% increase in body weight). Characteristics at enrollment were not different among the three groups, but mean differences in weight and percent changes in urinary sodium excretion over the period were statistically different (P < 0.001 and P =3D 0.017). Over the study period, unintentional weight loss independently increased the probability of reduced albuminuria (group 1, relative risk 6.234, 95% confidence interval 1.913-20.315, P =3D 0.002). Among urinary cytokines, only podocalyxin level decreased significantly in participants who lost weight (P =3D 0.013). Conclusion: We observed that weight loss had an additive effect on the anti-proteinuric effects of ARBs in nondiabetic hypertensive CKD patients, although it was minimal. An additive effect was shown in both obese and non-obese participants, and its possible mechanism is related to reduction of podocyte damage.
Oh, Se Won
Baek, Seon Ha
Kim, Yong Chul
Goo, Ho Suk
Heo, Nam Ju
Na, Ki Young
Chae, Dong Wan
Kim, Suhnggwon
Chin, Ho Jun
BACKGROUND: A recent collaborative meta-analysis by Kidney Disease: Improving Global Outcomes reported that an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) and an albumin-to-creatinine ratio of =E2=89=A5 10 mg/g were independent predictors for mortality in the general population. However, selection bias, heterogeneity of the cohorts and measurement issues could be limitations.; METHODS: We analyzed the relationship of eGFR and proteinuria with mortality in the Korean general population, represented by 112,115 participants, aged =E2=89=A5 20 years, who had a voluntary health check-up with homogenous calibration of creatinine measurement from 2003 to 2009. Proteinuria (trace or more) was determined by urine dipstick.; RESULTS: eGFR and proteinuria were independently associated with all-cause mortality (ACM) and cardiovascular mortality (CVM), and progressive increases in risks for mortality were noted according to eGFR level and the presence of proteinuria. Compared with eGFR 90-105 mL/min/1.73 m(2), hazard ratio (HRs) for ACM were 1.60 [95% confidence interval (CI) 1.12-2.30] for eGFR 60-74 mL/min/1.73 m(2) and 3.54 (2.20-5.68) for eGFR <60 mL/min/1.73 m(2) in participants with no proteinuria. In participants with proteinuria, HRs for ACM were 2.10 (1.41-3.12) for eGFR 75-89 mL/min/1.73 m(2), 2.30 (1.50-3.53) for eGFR 60-74 mL/min/1.73 m(2) and 3.77 (2.15-6.38) for eGFR <60 mL/min/1.73 m(2). Similar findings were observed for CVM.; CONCLUSIONS: eGFR <75 mL/min/1.73 m(2) and urine dipstick trace or more were independent risk factors of ACM and CVM. The risks of adverse outcomes are greater in the general population with mild renal impairment or mild proteinuria.=20
Baek, Seon Ha
Kim, Sejoong
Kim, Dong Ki
Park, Jung Hwan
Shin, Sung Joon
Lee, Sang Ho
Choi, Bum Soon
Chin, Ho Jun
Kim, Suhnggwon
Lim, Chun Soo
BACKGROUND/AIMS: An acid-base imbalance precedes renal disease progression in patients with chronic kidney disease (CKD). Little is known about the effects of a low-salt diet (LSD) on net endogenous acid production (NEAP) levels in CKD patients using angiotensin receptor blockade.; METHODS: We enrolled a total of 202 nondiabetic CKD patients who underwent an 8-week treatment with olmesartan from the original trial [Effects of Low Sodium Intake on the Antiproteinuric Efficacy of Olmesartan in Hypertensive Patients with Albuminuria (ESPECIAL) trial: NCT01552954]. The patients were divided into good- and poor-LSD-compliance groups.; RESULTS: During the interventional 8 weeks, the NEAP in the good-compliance group increased compared to the control group (12.9 =C2=B1 32.0 vs. -2.0 =C2=B1 35.0 mmol/day, p =3D 0.002). NEAP was positively associated with the good-LSD-compliance group in the fully adjusted analyses (r =3D 0.135, p =3D 0.016). The additional reduction of 2.39 g/day of protein intake with a reduction of 1 g/day of salt intake did not increase the NEAP under angiotensin II receptor blockade (ARB) treatment with an LSD (r =3D 0.546, p < 0.001).; CONCLUSION: We found that an LSD may increase the NEAP in nondiabetic CKD patients using ARB, which suggests that additional acid producing-protein restriction should be required to prevent the NEAP from rising. =C2=A9 2014 S. Karger AG, Basel.
Kim, Jang-Young
Son, Jung-Woo
Park, Sungha
Yoo, Tea-Hyun
Kim, Yong-Jin
Ryu, Dong-Ryeol
Chin, Ho Jun
BACKGROUND: Fimasartan is the ninth angiotensin receptor blocker to be developed. However, it has not yet been evaluated for reno-protective effects in hypertensive diabetic chronic kidney disease (CKD). The target blood pressure (BP) for hypertensive diabetic CKD is also a controversial topic. This trial was designed to assess the reno-protective effects of fimasartan compared to those of losartan as a primary outcome. This study also compares the two drugs with regard to cardiovascular and renal outcomes in accordance with target systolic BP (SBP) (as secondary outcomes).; METHODS: This study is a prospective, phase III, randomized, double-blind, active-controlled, non-inferiority, four-parallel group, dose-titration, multicenter trial. We recruit patients with hypertensive diabetic CKD with overt proteinuria. Participants will be randomized into four groups (1:1:1:1): fimasartan standard SBP control (SBP<140mmHg); fimasartan strict SBP control (SBP<130mmHg); losartan standard SBP control; and losartan strict SBP control. After 24weeks, all individuals are treated with fimasartan for an additional 120weeks in an open-label design, maintaining their assigned SBP control groups as randomized. The primary endpoint is the rate of change in proteinuria, which is assessed using the spot urine albumin-creatinine ratio at 24weeks. The secondary endpoints are the cardiovascular and renal outcomes at 144weeks compared between the strict SBP and standard SBP control groups.; DISCUSSION: The FANTASTIC is a clinical study to provide: (1) the reno-protective effect of fimasartan; and (2) the target BP to reduce adverse outcomes in hypertensive diabetic CKD with overt proteinuria.; TRIAL REGISTRATION: Clinicaltrials.gov, NCT02620306. Registered on 1 December 2015.=20
Chin, Ho Jun
Ahn, Jeong Myeong
Na, Ki Young
Chae, Dong-Wan
Lee, Tae Woo
Heo, Nam Joo
Kim, Suhnggwon
Methods. We selected 57 718 people who had undergone a routine health check-up. Results. The average CKD awareness was 3.1% (95% CI: 2.6-3.7%) and was increased with progressing CKD stage. The awareness was increased from 1.1% before the WKD campaign to 5.8% after the campaign (P < 0.001). CKD awareness in the post-WKD period was increased in CKD stages 2 (OR 4.535: 95% CI: 2.044-10.062) and 3 (OR 6.614: 95% CI: 4.282-10.217) and profoundly increased in stage 4 (OR 13.800: 95% CI: 2.127-89.524), compared to the pre-WKD period. In the CKD-aware group compared to the CKD-unaware group, the awareness of diabetes mellitus (90.0% versus 54.2%, P < 0.001) and hypertension (87.2% versus 64.7%, P < 0.001) was higher and the levels of systolic blood pressure (116.9 +/- 1.0 versus 120.1 +/- 0.2, P < 0.01) and serum cholesterol (198.3 +/- 2.7 versus 205.0 +/- 0.5, P < 0.05) were lower by covariance analysis. Conclusions. The WKD campaign had a positive impact on the awareness and control of risk factors in CKD subjects but the absolute frequency of CKD awareness still remains undesirable in Korea. We need new campaign strategies to publicize the importance of early diagnosis and appropriate management of CKD.
Kim, Yong-Chul
Chin, Ho Jun
Koo, Ho Suk
Kim, Suhnggwon
Background: Treatment remains uncertain for IgA nephropathy patients with mild to moderate proteinuria, for whom antihypertensive medication or the RAS blocker is not applicable due to low blood pressure. Trial design: A double blinded randomized trial. Methods: The anti-proteinuric effect of tacrolimus was explored for 40 biopsy-proven mild IgA nephropathies for 16 weeks. We randomly assigned patients either to receive tacrolimus or placebo with stratification by using a renin angiotensin system blocker. The primary outcome was the percentage change of final UACR compared to the baseline value (pcUACR). Results: The mean value of pcUACR at 12-week and 16-week visits (primary outcome) was decreased more in the Tac group compared to the control group (-52.0 +/- 26.4 vs -17.3 +/- 29.3%, p = 0.001). At each visit, pcUACR was also decreased more in the Tac group compared to the control group. In the Tac group, the pcUACRs were -60.2 +/- 28.2%, -62.2 +/- 33.9%, -48.5 +/- 29.8%, and -55.5 +/- 24.0%, and, in the control group, -6.8 +/- 32.2%, -2.5 +/- 35.9%, -12.7 +/- 34.2%, and -21.9 +/- 30.6%, at 4-week, 8-week, 12-week, and 16-week visits, respectively. The pre-defined secondary outcomes were better in the Tac group compared to the control group. The frequency of decrease in pcUACR and percentage change of UPCR (pcUPCR) >= 50% at 16 weeks were 65.0% (13/20) and 55.0% (11/20) in the Tac group, and 25.0% (5/20) and 15.0% (3/20), in the control group, respectively (p = 0.025 for pcUACR and p = 0.019 for pcUPCR). However, tacrolimus wasn't effective with a dose of 0.05 mg/kg/day in patients taking ARB. The adverse events were tolerable. Conclusion: Tacrolimus effectively reduced proteinuria in IgA nephropathy with normal blood pressure. This suggested that tacrolimus could be an alternative to corticosteroid and RAS blocker for IgA nephropathy patients who cannot endure antihypertensive medication.