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      Association of Serum Activin Levels with Allograft Outcomes in Patients with Kidney Transplant: Results from the KNOW-KT

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          Abstract

          Introduction: Serum activin A has been reported to contribute to vascular calcification and kidney fibrosis in chronic kidney disease. We aimed to investigate whether higher serum activin levels were associated with poor allograft outcomes in patients with kidney transplantation (KT). Methods: A total of 860 KT patients from KNOW-KT (Korean Cohort Study for Outcome in Patients with Kidney Transplantation) were analyzed. We measured serum activin levels pre-KT and 1 year after KT. The primary outcome was the composite of a ≥50% decline in estimated glomerular filtration rate and graft failure. Multivariable cause-specific hazard model was used to analyze association of 1-year activin levels with the primary outcome. The secondary outcome was coronary artery calcification score (CACS) at 5 years after KT. Results: During the median follow-up of 6.7 years, the primary outcome occurred in 109 (12.7%) patients. The serum activin levels at 1 year were significantly lower than those at pre-KT (488.2 ± 247.3 vs. 704.0 ± 349.6). When patients were grouped based on the median activin level at 1 year, the high-activin group had a 1.91-fold higher risk (95% CI, 1.25–2.91) for the primary outcome compared to the low-activin group. A one-standard deviation increase in activin levels as a continuous variable was associated with a 1.36-fold higher risk (95% CI, 1.16–1.60) for the primary outcome. Moreover, high activin levels were significantly associated with 1.56-fold higher CACS (95% CI, 1.12–2.18). Conclusion: Post-transplant activin levels were independently associated with allograft functions as well as coronary artery calcification in KT patients.

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          Long-term renal allograft survival in the United States: a critical reappraisal.

          Renal allograft survival has increased tremendously over past decades; this has been mostly attributed to improvements in first-year survival. This report describes the evolution of renal allograft survival in the United States where a total of 252 910 patients received a single-organ kidney transplant between 1989 and 2009. Half-lives were obtained from the Kaplan-Meier and Cox models. Graft half-life for deceased-donor transplants was 6.6 years in 1989, increased to 8 years in 1995, then after the year 2000 further increased to 8.8 years by 2005. More significant improvements were made in higher risk transplants like ECD recipients where the half-lives increased from 3 years in 1989 to 6.4 years in 2005. In low-risk populations like living-donor-recipients half-life did not change with 11.4 years in 1989 and 11.9 years in 2005. First-year attrition rates show dramatic improvements across all subgroups; however, attrition rates beyond the first year show only small improvements and are somewhat more evident in black recipients. The significant progress that has occurred over the last two decades in renal transplantation is mostly driven by improvements in short-term graft survival but long-term attrition is slowly improving and could lead to bigger advances in the future. ©2010 The Authors Journal compilation©2010 The American Society of Transplantation and the American Society of Transplant Surgeons.
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            Predictive value for the Chinese population of the Framingham CHD risk assessment tool compared with the Chinese Multi-Provincial Cohort Study.

            The Framingham Heart Study helped to establish tools to assess coronary heart disease (CHD) risk, but the homogeneous nature of the Framingham population prevents simple extrapolation to other populations. Recalibration of Framingham functions could permit various regions of the world to adapt Framingham tools to local populations. To evaluate the performance of the Framingham CHD risk functions, directly and after recalibration, in a large Chinese population, compared with the performance of the functions derived from the Chinese Multi-provincial Cohort Study (CMCS). The CMCS cohort included 30 121 Chinese adults aged 35 to 64 years at baseline. Participants were recruited from 11 provinces and were followed up for new CHD events from 1992 to 2002. Participants in the Framingham Heart Study were 5251 white US residents of Framingham, Mass, who were 30 to 74 years old at baseline in 1971 to 1974 and followed up for 12 years. "Hard" CHD (coronary death and myocardial infarction) was used as the end point in comparisons of risk factors (age, blood pressure, smoking, diabetes, total cholesterol, and high-density lipoprotein cholesterol [HDL-C]) as evaluated by the CMCS functions, original Framingham functions, and recalibrated Framingham functions. The CMCS cohort had 191 hard CHD events and 625 total deaths vs 273 CHD events and 293 deaths, respectively, for Framingham. For most risk factor categories, the relative risks for CHD were similar for Chinese and Framingham participants, with a few exceptions (ie, age, total cholesterol of 200-239 mg/dL [5.18-6.19 mmol/L], and HDL-C less than 35 mg/dL [0.91 mmol/L] in men; smoking in women). The discrimination using the Framingham functions in the CMCS cohort was similar to the CMCS functions: the area under the receiver operating characteristic curve was 0.705 for men and 0.742 for women using the Framingham functions vs 0.736 for men and 0.759 for women using the CMCS functions. However, the original Framingham functions systematically overestimated the absolute CHD risk in the CMCS cohort. For example, in the 10th risk decile in men, the predicted rate of CHD death was 20% vs an actual rate of 3%. Recalibration of the Framingham functions using the mean values of risk factors and mean CHD incidence rates of the CMCS cohort substantially improved the performance of the Framingham functions in the CMCS cohort. The original Framingham functions overestimated the risk of CHD for CMCS participants. Recalibration of the Framingham functions improved the estimates and demonstrated that the Framingham model is useful in the Chinese population. For regions that have no established cohort, recalibration using CHD rates and risk factors may be an effective method to develop CHD risk prediction algorithms suited for local practice.
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              Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era.

              Acute rejection is known to have a strong impact on graft survival. Many studies suggest that very low acute rejection rates can be achieved with current immunosuppressive protocols. We wanted to investigate how acute rejection rates have evolved on a national level in the U.S. and how this has impacted graft survival in the most recent era of kidney transplantation. For this purpose, we analyzed data provided by the Scientific Registry of Transplant Recipients regarding all adult first renal transplants between 1995 and 2000. We noted a significant decrease in overall acute rejection rates during the first 6 months, during the first year, and also in late rejections during the second year after transplantation. Despite this decrease in the rate of acute rejection, there was no significant improvement in overall graft survival; furthermore, we noted a statistically significant trend towards worse death-censored graft survival. There was also a trend for a greater proportion of rejection episodes to fail to recover to previous baseline function after treatment. Our data suggest that decreasing acute rejection rates between 1995 and 2000 have not led to an increase in long-term graft survival. Part of this discordance might be related to a higher proportion of acute rejections which have not resolved with full functional recovery in more recent years. However, the etiology of this concerning trend for worse death censored graft survival in recent years will warrant further investigation.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                Am J Nephrol
                S. Karger AG
                0250-8095
                1421-9670
                2024
                March 2024
                10 January 2024
                : 55
                : 2
                : 245-254
                Affiliations
                [a ]Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea
                [b ]Department of Internal Medicine, Ewha Womans University Medical Center, Seoul, Republic of Korea
                [c ]Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
                [d ]Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
                [e ]Department of Surgery, Sungkyunkwan University, Seoul Samsung Medical Center, Seoul, Republic of Korea
                [f ]Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
                [g ]Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea
                [h ]Department of Internal Medicine, Gachon University, Gil Hospital, Incheon, Republic of Korea
                [i ]Department of Internal Medicine, Keimyung University, Dongsan Medical Center, Daegu, Republic of Korea
                Author notes
                *Jaeseok Yang, jcyjs@yuhs.ac
                Article
                536198 Am J Nephrol 2024;55:245–254
                10.1159/000536198
                38198780
                62aa74fc-f84c-4421-80fb-5ebb6f0a8712
                © 2024 S. Karger AG, Basel
                History
                : 19 December 2023
                : 08 January 2024
                Page count
                Figures: 2, Tables: 4, Pages: 10
                Funding
                This research was supported by a fund (2012E3301100, 2013E3301600, 2013E3301601, 2013E3301602, 2016E3300200, 2016E3300201, 2016E3300202, 2019E320100, 2019E320101, 2019E320102, 2022-11-007) from the Research of Korea Disease Control and Prevention Agency.
                Categories
                Transplantation: Research Article

                Medicine
                Coronary artery calcification,Activin,Allograft failure,Biomarker,Kidney outcome,Kidney transplantation

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