Clinical Impact of Self-Recognition of Recurrent Acute Myocardial Infarction: From KRMI-RCC.

Background/Objectives: Self-recognition of recurrent myocardial infarction (re-MI) may be essential for reducing prehospital time contrast to awareness of re-MI symptoms. However, data on the current status and clinical impact of self-recognition of re-MI are limited in the contemporary period. Thus, this study aimed to increase this body of knowledge. Methods: We enrolled 1018 patients with re-MI using data from the Korean Registry of Acute Myocardial Infarction for Regional Cardiocerebrovascular Centres. The patients were classified into self-recognised MI and unrecognised MI groups, and the differences between them were compared. Results: The rate of self-recognition among the patients with previous experience of MI was only 52.4%. Among the patients with re-MI, factors associated with self-recognition included recent first MI within 3 years, prior dyslipidaemia, two or more MI symptoms, and the male gender (p < 0.05). Factors associated with a lack of recognition were older age (≥70 years), prior stroke, and cancer history (p < 0.05). The proportion of symptoms-to-emergency room arrival time within 90 min among the patients with ST-elevation MI was significantly higher in the self-recognised group than in the unrecognised group (52.6% vs. 31.6%, p < 0.001). The self-recognised group showed a lower in-hospital mortality rate (1.5% vs. 6.2%, p < 0.001), and this benefit was maintained even after 1 year (hazard ratio: 0.53; p < 0.001). Conclusions: Only half of the patients who previously experienced a MI recognised a re-MI when it occurred. This recognition reduced prehospital delay and led to higher survival rates, which highlights the importance of patient education as well as objective monitoring devices, irrespective of individual recognition ability for immediate response.

Hyperuricemia is a risk factor for the progression to end-stage renal disease in minimal change disease.

BACKGROUND: Minimal change disease (MCD) is one of the most common causes of nephrotic syndrome worldwide. Hyperuricemia increases the end-stage renal disease (ESRD) risk in glomerulonephritis. In this study, we aimed to determine the effect of high serum uric acid levels on the progression to ESRD in MCD. METHODS: A total of 800 patients diagnosed with MCD by kidney biopsy were retrospectively analyzed. We determined the relationship of hyperuricemia with the progression to ESRD in MCD using the Cox proportional hazard model and Kaplan-Meier survival analysis. The primary outcome was defined as the initiation of dialysis or kidney transplantation. RESULTS: A total of 42 patients (5.3%) progressed to ESRD during the follow-up period. In the restricted cubic spline curve, serum uric acid levels exhibited a positive correlation with ESRD progression in patients with MCD. In the fully adjusted model, the risk of MCD progression increased by 29% for every 1 mg/dL increase in the baseline serum uric acid level (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.09-1.54; p = 0.004). Falling into the high uric acid group (serum uric acid level > 7 mg/dL in men and > 6 mg/dL in women) was also a risk factor for progression of MCD to ESRD (HR, 3.40; 95% CI, 1.59-7.31; p < 0.001). CONCLUSION: Our study shows that hyperuricemia is an independent risk factor for the progression to ESRD in patients with MCD.

Increasing prescription of renin-angiotensin-aldosterone system blockers associated with improved kidney prognosis in Korean IgA nephropathy patients.

BACKGROUND: We aimed to describe the characteristics of immunoglobulin A nephropathy (IgAN) in Korea with assessment for time trends. METHODS: We performed a multicenter retrospective observational cohort study including biopsy-confirmed native IgAN cases from four tertiary hospitals in Korea. Time eras of diagnosis were stratified into 1979-2003, 2004-9 and 2010-17. The prognostic variable was progression to end-stage kidney disease (ESKD) analyzed by multivariable Cox regression analysis. RESULTS: We included 1366 (from 1979 to 2003), 1636 (from 2004 to 2009) and 1442 (from 2010 to 2017) IgAN patients in this study. In the recent periods, IgAN had relatively better clinical characteristics, as patients had higher estimated glomerular filtration rates and lower baseline blood pressures than before. The use of renin-angiotensin-aldosterone system (RAAS) blockers increased from 57.7% in 1979-2003 to 80.0% in 2010-17. During a median follow-up duration of 11.3 years, 722 patients progressed to ESKD with an incidence rate of 12.5 per 1000 person-years. The 10-year risk of progression to ESKD was lower in 2010-17 compared with that of 1979-2003 [adjusted hazard ratio 0.692 (95% confidence interval 0.523-0.915)], even after adjustment for multiple clinicopathologic characteristics. The use of RAAS blockers was a significant mediator (P < 0.001) for the association between time trends and lower 10-year ESKD risk. CONCLUSIONS: Clinicopathologic characteristics of IgAN in Korea have changed over time. Although the limitation of a retrospective observational study remains, the result showed that the prognosis of IgAN has improved over the study period, possibly related to increased prescription of RAAS blockers.

Small bowel ulcer bleeding due to suspected clopidogrel use in a patient with clopidogrel resistance: A case report.

BACKGROUND: Clopidogrel is a platelet aggregation inhibitor used for the management of cardiovascular disease. While antiplatelet therapy decreases cardiovascular events after successful coronary drug-eluting stenting, it increases the risk of gastrointestinal (GI) bleeding. About 20% of the patients who take clopidogrel exhibit resistance to the drug. CASE SUMMARY: We report the first case of a small bowel bleeding ulcer in an 86-year-old man with clopidogrel resistance. He had a history of taking clopidogrel due to unstable angina. There was no evidence of bleeding in the stomach, duodenum, or colon through upper and lower GI endoscopies. The abdominal computed tomography showed the extravasation of radiocontrast media at the ileum. Because of unstable vital signs, emergency surgery was performed. Multiple ulcers with inflammation were found in the ileum. The pathologic findings revealed simple inflammation. The VerifyNow P2Y12 test showed clopidogrel resistance. One year after changing to aspirin, capsule endoscopy was performed and the small bowel ulcers were improved. CONCLUSION: Small bowel ulcers and bleeding due to clopidogrel are not very common, but the prevalence is expected to increase in older age patients with risk factors despite clopidogrel resistance.

Systolic blood pressure and chronic kidney disease progression in patients with primary glomerular disease.

INTRODUCTION: Many current guidelines on optimal target blood pressure (BP) for chronic kidney disease (CKD) patients are largely based on studies in diabetic and hypertensive patients. However, there have been few studies in patients with glomerular diseases. METHODS: We retrospectively studied the longitudinal association between BP and CKD progression in 1,066 biopsy-proven patients diagnosed with primary glomerular diseases, including IgA nephropathy, membranous nephropathy (MN), and focal segmental glomerulosclerosis (FSGS), between 2005 and 2017. The main predictor was time-updated systolic blood pressure (SBP) at every clinic visit. The primary outcome was a composite one including ≥ 50% decrease in estimated glomerular filtration rate (eGFR) from the baseline, and end-stage kidney disease (ESKD). RESULTS: During 5009 person-years of follow-up, the primary outcome occurred in 157 (14.7%) patients. In time-varying Cox model, the adjusted hazard ratios (HRs) (95% confidence interval (CI)) for the primary outcome were 1.48 (0.96-2.29), 2.07 (1.22-3.52), and 2.53 (1.13-5.65) for SBP of 120-129, 130-139, and ≥ 140 mmHg, respectively, compared with SBP < 120 mmHg. This association was particularly evident in patients with elevated proteinuria. However, there was no association between baseline SBP and adverse kidney outcomes. Finally, prediction models failed to show the improvement of predictive performance of SBP compared with that of remission status. Moreover, patients with remission and less controlled SBP had better kidney outcomes than those with non-remission and well-controlled SBP. CONCLUSION: Among patients with glomerular disease, higher time-updated SBP was significantly associated with higher risk of CKD progression. However, the clinical significance of blood pressure was less powerful than remission status.

Association of Mortality with Antiplatelet Treatment in Patients with Stent Placement or Angioplasty: A Population-Based Nested Case-Control Study.

PURPOSE: Antiplatelet drugs are essential in patients with cardiovascular disease who undergo stent placement. We hypothesized that risks of mortality would differ according to adherence to antiplatelet agents, number of antiplatelet agents, and antiplatelet regimens in patients undergoing stent placement or angioplasty. MATERIALS AND METHODS: Between 2002 and 2013, we initially enrolled 8671 subjects who underwent stent placement or angioplasty in the National Health Insurance Service-National Sample Cohort in Korea. Using the International Classification of Diseases, 10th revision, the incidence of all-cause death, including cardiovascular disease, cerebrovascular disease, and cancer, was defined. Using a nested case-control study design, controls were matched to cases at a ratio of 4:1, and a total of 5415 subjects were eligible for this study. RESULTS: During a median follow-up period of 3.51 years, the incidence rate of all-cause death was 40 per 1000 person-years. We found that adherence to antiplatelet monotherapy significantly decreased risk of death by cerebro-cardiovascular disease, compared with discontinuation of antiplatelets [adjusted odds ratio (OR) 0.62, 95% confidence interval (CI) (0.41-0.96)]. Compared with dual antiplatelet therapy (DAPT), aspirin and clopidogrel monotherapy significantly reduced death by cerebro-cardiovascular disease [adjusted OR 0.65, 95% CI (0.44-0.95) and adjusted OR 0.58, 95% CI (0.35-0.96), respectively]. There was no significant difference of mortality between aspirin monotherapy and clopidogrel monotherapy. CONCLUSION: Our study demonstrated that adherence to antiplatelet therapy and antiplatelet monotherapy, compared with DAPT, in patients with stent placement or angioplasty may have a beneficial effect on mortality in cerebro-cardiovascular disease.

Radiation exposure of interventional cardiologists during coronary angiography: evaluation by phantom measurement and computer simulation.

During interventional cardiological procedures, operators are exposed to patients' scatter radiation. Therefore, we measured the radiation exposure of the operator's eyeball, thyroid, and chest wall during angiography. We used the optically stimulated luminescence dosimeter in the anthropomorphic phantom and developed Monte Carlo simulations using the Korean human voxel phantom. At 15 frames/s, the radiation dose of the operator's right eyeball (RE), left eyeball (LE), thyroid (T), and chest wall (CW) at the femoral artery puncture position (FAPP) with protective equipment (PE) was 0.015, 0.16, 0.012, and 0.014 mGy, respectively. At 7.5 frames/sec, the radiation dose of the operator's RE, LE, T, and CW at FAPP with PE was 33.33%, 18.75%, 52.94%, and 45.00% lower than that of those at the radial artery puncture position (RAPP), respectively. At 15 frames/s, the radiation dose of the operator's RE, LE, T, and CW at RAPP without PE was 1.76 times, 2.23 times, 2.76 times, and 2.05 times higher than that of those with PE. Per the simulation results, the absorbed radiation dose of the eye ball, thyroid gland, and myocardium of the heart at FAPP with and without PE under 15 frame/s was 9.68%, 13.04%, 8.33% and 9.98%, 6.00%, 8.82% lower than at RAPP under similar conditions. Effective measures for occupational radiological protection are lower frame rate exposure, increased distance from the X-ray source, and PE use. Radiologist protection in interventional cardiology cannot be handled independently of patient protection, owing to several correlations; thus, reducing the patient dose will reduce the operator dose.

Biobanking for glomerular diseases: a study design and protocol for KOrea Renal biobank NEtwoRk System TOward NExt-generation analysis (KORNERSTONE).

BACKGROUNDS: Glomerular diseases, a set of debilitating and complex disease entities, are related to mortality and morbidity. To gain insight into pathophysiology and novel treatment targets of glomerular disease, various types of biospecimens linked to deep clinical phenotyping including clinical information, digital pathology, and well-defined outcomes are required. We provide the rationale and design of the KOrea Renal biobank NEtwoRk System TOward Next-generation analysis (KORNERSTONE). METHODS: The KORNERSTONE, which has been initiated by Korea Centres for Disease Control and Prevention, is designed as a multi-centre, prospective cohort study and biobank for glomerular diseases. Clinical data, questionnaires will be collected at the time of kidney biopsy and subsequently every 1 year after kidney biopsy. All of the clinical data will be extracted from the electrical health record and automatically uploaded to the web-based database. High-quality digital pathologies are obtained and connected in the database. Various types of biospecimens are collected at baseline and during follow-up: serum, urine, buffy coat, stool, glomerular complementary DNA (cDNA), tubulointerstitial cDNA. All data and biospecimens are processed and stored in a standardised manner. The primary outcomes are mortality and end-stage renal disease. The secondary outcomes will be deterioration renal function, remission of proteinuria, cardiovascular events and quality of life. DISCUSSION: Ethical approval has been obtained from the institutional review board of each participating centre and ethics oversight committee. The KORNERSTONE is designed to deliver pioneer insights into glomerular diseases. The study design allows comprehensive, integrated and high-quality data collection on baseline laboratory findings, clinical outcomes including administrative data and digital pathologic images. This may provide various biospecimens and information to many researchers, establish the rationale for future more individualised treatment strategies for glomerular diseases. TRIAL REGISTRATION: NCT03929887 .

Efficacy and Safety of a Balanced Salt Solution Versus a 0.9% Saline Infusion for the Prevention of Contrast-Induced Acute Kidney Injury After Contrast-Enhanced Computed Tomography.

RATIONALE & OBJECTIVE: We aimed to elucidate whether a balanced salt solution decreases the occurrence of contrast-induced acute kidney injury (CI-AKI) after contrast-enhanced computed tomography (CE-CT) as compared to 0.9% saline solution. STUDY DESIGN: A randomized clinical trial. SETTING & PARTICIPANTS: The study was performed in 14 tertiary hospitals in South Korea. Patients with estimated glomerular filtration rates (eGFRs) < 45 or <60 mL/min/1.73 m2 and additional risk factors (age ≥ 60 years or diabetes) who were undergoing scheduled CE-CT were included from December 2016 to December 2018. INTERVENTION: An open-label intervention was performed. The study group received a balanced salt solution and the control group received 0.9% saline solution as prophylactic fluids for CE-CT. OUTCOMES: The primary outcome was CI-AKI, defined by creatinine level elevation ≥ 0.5 mg/dL or 25% from baseline within 48 to 72 hours after CE-CT. Secondary outcomes included AKI defined based on the KDIGO (Kidney Disease: Improving Global Outcomes) guideline, eGFR changes, death, or requiring dialysis within 6 months after CE-CT. RESULTS: 493 patients received the study fluids. The control and study groups included 251 and 242 patients, respectively. The occurrence of CI-AKI in the study (10 [4.2%]) and control (17 [6.8%]) groups was not significantly different (P = 0.27). No significant difference was present for the secondary outcomes; AKI by the KDIGO definition (study: 19 [7.9%], control: 27 [10.8%]; P = 0.33), death/dialysis (study: 11 [4.7%], control: 9 [3.7%]; P = 0.74), and eGFR changes (study: 0.1 ± 0.2 mg/dL, control: 0.3 ± 2.8 mg/dL; P = 0.69). LIMITATIONS: This study failed to meet target enrollment. CONCLUSIONS: The risk for CI-AKI was similar after administration of a balanced salt solution and after use of 0.9% saline solution during CE-CT in higher-risk patients. FUNDING: This study was funded by CJ Healthcare (CS2015_0046). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT02799368.

The Combined Impact of Chronic Kidney Disease and Diabetes on the Risk of Colorectal Cancer Depends on Sex: A Nationwide Population-Based Study.

PURPOSE: Although both chronic kidney disease (CKD) and diabetes mellitus (DM) are considered factors increasing the risk of colorectal cancer (CRC), their impact on CRC is not fully understood. This study was aimed to investigate the impact of CKD, DM, or both diseases on the risk of CRC and to evaluate sex differences therein. MATERIALS AND METHODS: Using data from the National Health Insurance Service-Health Examination Cohort in Korea, we conducted a 1:2 matched case-control study. The disease groups consisted of CKD-/DM+ (n=17700), CKD+/DM- (n=22643), and CKD+/DM+ groups (n=8506). After 1:2 matching by age, sex, and health examination year and month, the healthy control group consisted of 97698 individuals. RESULTS: Multivariate Cox regression analysis showed that the CKD-/DM+, CKD+/DM-, and CKD+/DM+ groups were independently associated with an increased incidence of CRC, compared with controls [hazard ratio (HR), 1.34, 1.31, and 1.63, respectively; all p<0.001]. Compared to the controls, adjusted HRs for the cumulative incidence of CRC in the CKD-/DM+, CKD+/DM-, and CKD+/DM+ groups were, respectively, 1.32, 1.26, and 1.43 in male and 1.38, 1.39, and 2.00 in female. The HR for CRC incidence was significantly higher for the CKD+/DM+ group than for the CKD-/DM+ or CKD+/DM- group in female; however, this significant difference was not observed in male. CONCLUSION: In female, having both CKD and DM significantly increases the risk of CRC, compared with having CKD or DM alone. This study suggests a significant difference in the effect of CKD or DM on the risk of CRC according to sex.

Motion microscopy for label-free detection of circulating breast tumor cells.

Circulating tumor cells (CTCs) are cancer cells that have been shed from a primary tumor and circulate in the bloodstream during progression of cancer. They may thus serve as circulating biomarkers that can predict, diagnose and guide therapy. Moreover, phenotypic and genotypic analysis of CTCs can facilitate prospective assessment of mutations and enable personalized treatment. A number of methodologies based on biological and physical differences between circulating tumor and non-tumor cells have been developed over the past few years. However, these methods did not have sufficient sensitivity or specificity. In this work, a remote analysis protocol was designed using motion microscopy that amplifies cellular micro motions in a captured video by re-rendering small motions to generate extreme magnified visuals to detect dynamic motions that are not otherwise visible by naked eye. Intriguingly, motion microscopy demonstrated fluctuations around breast tumor cells, which we referred to herein as cellular trail. Phenomena of cellular trail mostly emerged between 0.5 and 1.5 Hz on amplified video images. Interestingly, cellular trails were associated with cell surface proteins and flow rates rather than mitochondrial activity. Moreover, cellular trails were present only around circulating tumor cells from individuals with breast cancer under conditions of 20-30 µm/s and 0.5-1.5 Hz. Thus, motion microscopy based CTC detection method can offer a valuable supplementary diagnostic tool for assessment of drug efficacy and identifying physical characteristics of tumor cells for further research.

Occupational radiation exposure in femoral artery approach is higher than radial artery approach during coronary angiography or percutaneous coronary intervention.

Medical radiation exposure is a significant concern for interventional cardiologists (IC). This study was aimed at estimating the radiation exposure of IC operators and assistants in real clinical practice. The radiation exposure of the operator and assistant was evaluated by conducting two types of procedures via coronary angiography (CAG) and percutaneous coronary intervention (PCI) on 1090 patients in 11-cardiovascular centers in Korea. Radiation exposure was measured using an electronic personal dosimeter (EPD). EPD were attached at 3 points on each participant: on the apron on the left anterior chest (A1), under the apron on the sternum (A2), and on the thyroid shield (T). Average radiation exposure (ARE) of operators at A1, A2, and T was 19.219 uSv, 4.398 uSv, and 16.949 uSv during CAG and 68.618 uSv, 15.213 uSv, and 51.197 uSv during PCI, respectively. ARE of assistants at A1, A2, and T was 4.941 uSv, 0.860 uSv, and 5.232 uSv during CAG and 20.517 uSv, 4.455 uSv, and 16.109 uSv during PCI, respectively. AED of operator was 3.4 times greater during PCI than during CAG.

Serum Uric Acid is Associated with Renal Prognosis of Lupus Nephritis in Women but not in Men.

Lupus nephritis (LN) is a major complication of systemic lupus erythematosus. Early intervention in lupus nephritis improves prognosis. There is an association between hyperuricemia and lupus nephritis; nevertheless, the sex-specific role of uric acid in lupus nephritis remains unclear. We retrospectively analyzed 578 patients diagnosed with LN by renal biopsy. We determine the relationship of serum uric acid to progression of LN using Kaplan-Meier survival analyses and Cox proportional hazards models. The primary end point was LN progression defined as the initiation of dialysis or kidney transplantation. Men had higher mean serum uric acid levels than did women. Every 1 mg/dL increase in baseline uric acid level increased the risk of LN progression by 15.1%. The serum uric acid level was an independent risk factor for LN progression in women (hazard ratio [HR], 1.158; confidence interval [CI], 1.018-1.317; p = 0.028) but not in men (HR, 1.499; CI, 0.964-2.331; p = 0.072). Sensitivity analysis involving serum uric acid terciles generated consistent and robust results. Serum uric acid level was an independent risk factor for LN progression in women but not in men.

Predictive value of mesangial C3 and C4d deposition in IgA nephropathy.

We aimed to determine the relative contribution of each complement (C3 and C4d) deposition to the progression of IgA nephropathy (IgAN). We enrolled a total of 380 patients with biopsy-confirmed IgAN. Mesangial deposition of C3(<2+ vs. ≥2+) and C4d(positive vs. negative) was evaluated by immunofluorescence staining and immunohistochemistry, respectively. Study endpoint was the composite of a 30% decline in eGFR or ESRD. The risk of reaching the primary outcome was significantly higher in patients having C3 ≥ 2+ and C4d(+) than in corresponding counterparts. Adding C3 deposition to clinical data acquired at kidney biopsy modestly increased the area under the receiver-operating characteristic curve, net reclassification improvement, and integrated discrimination improvement (IDI); adding C4d increased IDI only. In conclusion, mesangial C3 and C4d deposition was an independent risk factor for progression of IgAN. C3 showed better predictability than C4d, suggesting that lectin pathway alone has limited clinical prognostic value.

Relationship between complement deposition and the Oxford classification score and their combined effects on renal outcome in immunoglobulin A nephropathy.

BACKGROUND: Complement activation has been highlighted in immunoglobulin (Ig) A nephropathy pathogenesis. However, whether the complement system can affect the downstream phenotype of IgA nephropathy remains unknown. Herein, we investigated the association of mesangial C3 deposition with the Oxford classification and their joint effects on worsening kidney function. METHODS: We investigated 453 patients with biopsy-proven IgA nephropathy. C3 deposition was defined as an immunofluorescence intensity of C3 ≥2+ within the mesangium. The subjects were classified according to the combination of C3 deposition and Oxford classification lesions. The primary endpoint was a composite of ≥30% decline in the estimated glomerular filtration rate or an increase in proteinuria ≥3.5 g/g during follow-up. RESULTS: Among the Oxford classification lesions, mesangial hypercellularity (M1), segmental glomerulosclerosis (S1) and tubulointerstitial fibrosis (T1-2) and crescentic lesion significantly correlated with C3 deposition. During a median follow-up of 33.0 months, the primary endpoint occurred more in patients with M1, S1, T1-2 and mesangial C3 deposition than in those without. In individual multivariable-adjusted Cox analyses, the presence of M1, S1, T1-2 and C3 deposition was significantly associated with higher risk of reaching primary endpoint. In the combined analyses of C3 deposition and the Oxford classification lesions, the hazard ratios for the composite outcome were significantly higher in the presence of C3/M1, C3/S1 and C3/crescent than in the presence of each lesion alone. CONCLUSIONS: Complement deposition can strengthen the significance of the Oxford classification, and the presence of both components portends a poorer prognosis in IgA nephropathy.

The protective effect of klotho against contrast-associated acute kidney injury via the antioxidative effect.

As oxidative stress is one major factor behind contrast-associated acute kidney injury (CA-AKI), we investigated the protective effect of klotho against CA-AKI via the antioxidative effect. In in vitro experiments, cells (NRK-52E) were divided into the following three groups: control, iopamidol, or iopamidol + recombinant klotho (rKL) groups. Moreover, cell viability was measured with the Cell Counting Kit-8 assay, and oxidative stress was examined with 2',7'-dichlorodihydrofluorescein diacetate fluorescence intensity. RT-PCR and Western blot analysis were performed to assess propidium iodide klotho expression, and Bax-to-Bcl-2 and apoptosis ratios were evaluated with annexin V/Hoechst 33342 staining. Furthermore, we knocked down the klotho gene using siRNA to verify the endogenous effect of klotho. In our in vivo experiments, oxidative stress was evaluated with the thiobarbituric acid-reactive substance assay, and apoptosis was evaluated with the Bax-to-Bcl-2 ratio and cleaved caspase-3 immunohistochemistry. Additionally, cell and tissue morphology were investigated with transmission electron microscopy. In both in vitro and in vivo experiments, mRNA and protein expression of klotho significantly decreased in CA-AKI mice compared with control mice, whereas oxidative stress and apoptosis markers were significantly increased in CA-AKI mice. However, rKL supplementation mitigated the elevated apoptotic markers and oxidative stress in the CA-AKI mouse model and improved cell viability. In contrast, oxidative stress and apoptotic markers were more aggravated when the klotho gene was knocked down. Moreover, we found more cytoplasmic vacuoles in the CA-AKI mouse model using transmission electron microscopy but fewer cytoplasmic vacuoles in rKL-supplemented cells. The present study shows that klotho in proximal tubular cells can protect against CA-AKI via an antioxidative effect.

The Effect of Aspirin on Preventing Vascular Access Dysfunction in Incident Hemodialysis Patients: A Prospective Cohort Study in Korean Clinical Research Centers for End-Stage Renal Disease (CRC for ESRD).

Background: Aspirin is often prescribed empirically to improve the patency of hemodialysis (HD) vascular access. Therefore, this study aimed to investigate the impact of aspirin on the survival of vascular access in incident HD patients with arteriovenous fistula (AVF) or arteriovenous graft (AVG). Methods: A prospective cohort of 881 incident HD patients was enrolled between 2009 and 2014. The primary outcome was defined as the first AVF/AVG intervention or salvage procedure, including percutaneous transluminal angioplasty or surgery for vascular access failure. Cox analyses were performed to determine the association between aspirin usage and the occurrence of the primary outcome. Results: The mean age of the patient group was 57.9 ± 13.4, and 63.8% of the patients were male. Aspirin was prescribed in 241 (27.4%) patients, and the median follow-up duration was 30 months. During follow-up, 180 (20.4%) patients experienced the primary outcome event. Univariate analysis showed that age, gender, presence of diabetes mellitus (DM), preexisting peripheral arterial disease, and the type of vascular access used (AVG versus AVF) were significantly associated with the development of the primary outcome. However, aspirin usage from the baseline was not significantly associated with primary outcome events (hazard ratio (HR): 1.16; 95% confidence interval (CI): 0.84-1.60; p = 0.378). Multivariate analysis showed that gender, the presence of DM, and the type of vascular access were still significantly associated with the occurrence of the primary outcome. Moreover, we did not observe the protective effect of taking aspirin on primary vascular access failure, even in subgroup analyses stratified according to gender, the presence of DM, and the type of vascular access. Conclusion: Physicians should carefully consider when they prescribe aspirin for the prevention of primary vascular access failure in Korean incident HD patients. In addition, larger prospective interventional studies are needed to elucidate the effect of aspirin on vascular access failure.

C1q nephropathy in adults is a form of focal segmental glomerulosclerosis in terms of clinical characteristics.

Although C1q nephropathy (C1qN) was introduced three decades ago, the clinical significance and renal outcomes of C1qN remain unclear. This study aimed to evaluate the clinical characteristics of C1qN, including renal outcomes, by performing a matched comparison within a multicenter cohort. We enrolled 6,413 adult patients who underwent kidney biopsy between January 2000 and January 2018 at three tertiary hospitals in Korea. We compared the clinical characteristics of 23 patients with C1qN with those of patients with focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) who were matched by age, sex, diabetic status, and a period of biopsy. Histological and clinical parameters in patients with C1qN were also evaluated according to the different pathological phenotypes. For a mean follow-up period of 92 months, 4 patients with C1qN (17.4%) developed end-stage renal disease (ESRD). None of the matched patients with MCD had ESRD, but 7 (30.4%) of patients with FSGS progressed to ESRD, which was not different from that of C1qN patients (p = 0.491). Laboratory and pathological findings, except segmental glomerulosclerosis, were not notably different between FSGS and C1qN. The presence of segmental glomerulosclerosis, mesangial hypercellularity, and podocyte effacement did not affect both the short- and long-term renal outcomes in patients with C1qN. Our study showed that the renal outcomes of C1qN are comparable with those of FSGS, and not with MCD. Specific pathological findings, including segmental glomerulosclerosis in C1qN, were not associated with renal outcomes, which may suggest homogeneity in the clinical features of C1qN.

Clinical Significance of Crescent Formation in IgA Nephropathy - a Multicenter Validation Study.

BACKGROUND/AIMS: Additional validation study was warranted to confirm the clinical significance of C score, which was recently added to the Oxford classification for immunoglobulin A nephropathy (IgAN). METHODS: We performed a multicenter retrospective cohort study in four hospitals in Korea. Patients who had biopsied glomeruli less than eight or inadequate follow-up information were excluded. Clinicopathologic parameters, including the degree of cellular or fibrocellular crescents, were collected and included in multivariable models for Cox regression analysis. The main outcome was a composite renal outcome, defined as a merge of progression to end-stage renal disease (ESRD) and halving of estimated glomerular filtration rate (eGFR) from baseline. RESULTS: Among included 3,380 biopsy-confirmed IgAN patients, there were 664 (19.6%) patients with C1 and 60 (1.8%) patients with C2 scores in the study population. Although C0 and C1 patients shared similar baseline characteristics, C2 patients frequently had more clinicopathologic risk factors for poor prognosis of IgAN. Both C1 [adjusted HR 1.33 (1.11-1.58), P=0.002] and C2 [adjusted HR 2.24 (1.46-3.43), P< 0.001] scores were associated with an increased risk of the composite outcome. C2 was a strong predictive parameter associated with both progression to ESRD and halving of eGFR, whereas C1 was mainly associated with the increased risk of halving of eGFR. Notably, the proportion of crescent showed a linear association with the risk of adverse renal outcome. CONCLUSION: The C score in the Oxford classification is a valid predictive parameter for IgAN prognosis. Additional clinical attention is necessary for IgAN patients with identified cellular or fibrocellular crescents.

Sirt1-hypoxia-inducible factor-1α interaction is a key mediator of tubulointerstitial damage in the aged kidney.

Although it is known that the expression and activity of sirtuin 1 (Sirt1) decrease in the aged kidney, the role of interaction between Sirt1 and hypoxia-inducible factor (HIF)-1α is largely unknown. In this study, we investigated whether HIF-1α could be a deacetylation target of Sirt1 and the effect of their interaction on age-associated renal injury. Five-week-old (young) and 24-month-old (old) C57Bl/6J mice were assessed for their age-associated changes. Kidneys from aged mice showed increased infiltration of CD68-positive macrophages, higher expression of extracellular matrix (ECM) proteins, and more apoptosis than young controls. They also showed decreased Sirt1 expression along with increased acetylated HIF-1α. The level of Bcl-2/adenovirus E1B-interacting protein 3, carbonic anhydrase 9, Snail, and transforming growth factor-ß1, which are regulated by HIF-1α, was significantly higher in aged mice suggesting that HIF-1α activity was increased. In HK-2 cells, Sirt1 inhibitor sirtinol and siRNA-mediated knockdown of Sirt1 enhanced apoptosis and ECM accumulation. During hypoxia, Sirt1 was down-regulated, which allowed the acetylation and activation of HIF-1α. Resveratrol, a Sirt1 activator, effectively prevented hypoxia-induced production of ECM proteins, mitochondrial damage, reactive oxygen species generation, and apoptosis. The inhibition of HIF-1α activity by Sirt1-induced deacetylation of HIF-1α was confirmed by Sirt1 overexpression under hypoxic conditions and by resveratrol treatment or Sirt1 overexpression in HIF-1α-transfected HK-2 cells. Finally, we confirmed that chronic activation of HIF-1α promoted apoptosis and fibrosis, using tubular cell-specific HIF-1α transgenic mice. Taken together, our data suggest that Sirt1-induced deacetylation of HIF-1α may have protective effects against tubulointerstitial damage in aged kidney.