Physical Fitness as a Prognostic Marker for Infectious Events in Kidney Transplant Recipients

2021 ◽  
pp. 1-9
Author(s):  
Sara Ortolan ◽  
Daniel Neunhaeuserer ◽  
Francesca Battista ◽  
Alessandro Patti ◽  
Stefano Gobbo ◽  
...  
Keyword(s):  
Muscle Strength ◽  
Kidney Transplant ◽  
Cox Regression ◽  
Hemoglobin Concentration ◽  
Cardiopulmonary Exercise Test ◽  
Peak Oxygen Consumption ◽  
Healthy Population ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Isometric Handgrip

<b><i>Introduction:</i></b> Infectious events are one of the leading causes of death in kidney transplant recipients (KTRs). KTRs have reduced cardiorespiratory fitness (CRF), a predictor for infections in other populations. The aim of this study was to investigate whether CRF and muscle strength are prognostic markers for infectious events in KTRs. <b><i>Methods:</i></b> In this retrospective cohort study, 155 KTRs underwent an incremental, maximal cardiopulmonary exercise test (CPET) 3 months after transplantation. CRF was analyzed with peak oxygen consumption (VO<sub>2</sub> peak) while muscle strength with isometric handgrip (HG) test. Laboratory blood samples and drug therapy were collected. The median follow-up period was 54 (interquartile range 38–62) months. Cox regression analyses were performed to evaluate predictors of infectious events adjusting for potential confounders. <b><i>Results:</i></b> During this study, severe infectious events occurred in 41 subjects (26.5%). 15.5% (<i>n</i> = 24) of patients had a severely reduced CRF, defined as a VO<sub>2</sub> peak below the 5th percentile of the reference values reported for a matched healthy population. The hazard ratio for infectious events in this subgroup was 2.389 (95% CI = 1.188–4.801, <i>p</i> = 0.014), independently of gender, age, BMI, time on dialysis, hemoglobin concentration, eGFR, diabetes, and immunosuppressive regimen. On the contrary, no significant association of HG strength and infections was found. <b><i>Conclusion:</i></b> Therefore, low CRF may be considered as a modifiable predictor of severe infectious events in KTRs. A CPET should thus be recommended for cardiovascular screening, evaluation of CRF, and tailored exercise prescription to reduce the risk of infections and potentially improve long-term outcomes of transplantation.

scholarly journals Urinary Carnosinase-1 Excretion is Associated with Urinary Carnosine Depletion and Risk of Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Cohort Study

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1102
Author(s):  
Angelica Rodriguez-Niño ◽  
Diego O. Pastene ◽  
Adrian Post ◽  
M. Yusof Said ◽  
Antonio W. Gomes-Neto ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Failure ◽  
Cox Regression ◽  
Carbonyl Stress ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Increased Risk ◽  
High Concentrations ◽  
Kidney Function Decline

Carnosine affords protection against oxidative and carbonyl stress, yet high concentrations of the carnosinase-1 enzyme may limit this. We recently reported that high urinary carnosinase-1 is associated with kidney function decline and albuminuria in patients with chronic kidney disease. We prospectively investigated whether urinary carnosinase-1 is associated with a high risk for development of late graft failure in kidney transplant recipients (KTRs). Carnosine and carnosinase-1 were measured in 24 h urine in a longitudinal cohort of 703 stable KTRs and 257 healthy controls. Cox regression was used to analyze the prospective data. Urinary carnosine excretions were significantly decreased in KTRs (26.5 [IQR 21.4–33.3] µmol/24 h versus 34.8 [IQR 25.6–46.8] µmol/24 h; p < 0.001). In KTRs, high urinary carnosinase-1 concentrations were associated with increased risk of undetectable urinary carnosine (OR 1.24, 95%CI [1.06–1.45]; p = 0.007). During median follow-up for 5.3 [4.5–6.0] years, 84 (12%) KTRs developed graft failure. In Cox regression analyses, high urinary carnosinase-1 excretions were associated with increased risk of graft failure (HR 1.73, 95%CI [1.44–2.08]; p < 0.001) independent of potential confounders. Since urinary carnosine is depleted and urinary carnosinase-1 imparts a higher risk for graft failure in KTRs, future studies determining the potential of carnosine supplementation in these patients are warranted.

scholarly journals P1706THE GRAFT SURVIVAL OF KIDNEY TRANSPLANTATION ACCORDING TO ETHNICITY IN KIDNEY TRANSPLANT RECIPIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yeonsoon Jung ◽  
Jisu Kim ◽  
Haesu Jeon ◽  
Ye Na Kim ◽  
Ho Sik Shin ◽  
...  
Keyword(s):  
African American ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Cox Regression ◽  
Patient Survival ◽  
Graft Loss ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Data Set

Abstract Background African American kidney transplant recipients experience disproportionately high rates of graft loss. The aim of this analysis was to use a UNOS data set that contains detailed baseline and longitudinal clinical data to establish and quantify the impact of the current overall graft loss definition on suppressing the true disparity magnitude in US AA kidney transplant outcomes. Methods Longitudinal cohort study of kidney transplant recipients using a data set created by United Network for Organ Sharing (UNOS), including 266,128 (African American 70,215, Non-African American 195,913) transplant patient between 1987 and December 2016. Multivariable analysis was conducted using 2-stage joint modeling of random and fixed effects of longitudinal data (linear mixed model) with time to event outcomes (Cox regression). Results 195,913 non-African American (AA) (73.6%) were compared with 70,215 AA (26.4%) recipients. 10-year-graft survival of AA in all era is lower than that of non-AA (31% in deceased kidney transplants (DKT) AA recipient and 42% in living kidney transplantation (LKT) non-AA recipient). 10-year-patient survival of AA with functioning graft in all era is similar that of non-AA. Multivariate Cox regression of factors associated with patient survival with functioning graft are acute rejection within 6 months, DM, hypertension and etc. Pre-transplant recipient BMI in AA show the trend as a protective factor in patient survival with functioning graft although not significantly in statistics Conclusions African American kidney transplant recipients experience a substantial disparity in graft loss, but not patient death with functioning graft.

scholarly journals Sclerostin is an independent risk factor for all-cause mortality in kidney transplant recipients

2020 ◽  
Vol 24 (12) ◽  
pp. 1177-1183
Author(s):  
Shufei Zeng ◽  
Torsten Slowinski ◽  
Wolfgang Pommer ◽  
Ahmed A. Hasan ◽  
Mohamed M. S. Gaballa ◽  
...  
Keyword(s):  
Risk Factor ◽  
Renal Transplant ◽  
Kidney Transplant ◽  
Independent Risk Factor ◽  
Cox Regression ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Kaplan Meier ◽  
All Cause Mortality

Abstract Background Sclerostin is a hormone contributing to the bone-vascular wall cross talk and has been implicated in cardiovascular events and mortality in patients with chronic kidney disease (CKD). We analyzed the relationship between sclerostin and mortality in renal transplant recipients. Methods 600 stable renal transplant recipients (367men, 233 women) were followed for all-cause mortality for 3 years. Blood and urine samples for analysis and clinical data were collected at study entry. We performed Kaplan–Meier survival analysis and Cox regression models considering confounding factors such as age, eGFR, cold ischemia time, HbA1c, phosphate, calcium, and albumin. Optimal cut-off values for the Cox regression model were calculated based on ROC analysis. Results Sixty-five patients died during the observation period. Nonsurvivors (n = 65; sclerostin 57.31 ± 30.28 pmol/L) had higher plasma sclerostin levels than survivors (n = 535; sclerostin 47.52 ± 24.87 pmol/L) (p = 0.0036). Kaplan–Meier curve showed that baseline plasma sclerostin concentrations were associated with all-cause mortality in stable kidney transplant recipients (p = 0.0085, log-rank test). After multiple Cox regression analysis, plasma levels of sclerostin remained an independent predictor of all-cause mortality (hazard ratio, 1.011; 95% CI 1.002–1.020; p = 0.0137). Conclusions Baseline plasma sclerostin is an independent risk factor for all-cause mortality in patients after kidney transplantation.

scholarly journals The Risk of Stroke in Kidney Transplant Recipients with End-Stage Kidney Disease

2019 ◽  
Vol 16 (3) ◽  
pp. 326 ◽  
Author(s):  
Shih-Ting Huang ◽  
Tung-Min Yu ◽  
Ya-Wen Chuang ◽  
Mu-Chi Chung ◽  
Chen-Yu Wang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
General Population ◽  
Kidney Transplant ◽  
Lower Risk ◽  
Cox Regression ◽  
Research Database ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Increased Risk ◽  
End Stage

Background: The incidence of stroke after kidney transplantation is poorly understood. Our study aimed to determine the incidence and predictors of stroke as well as mortality from stroke in kidney transplant recipients (KTRs). Methods: This retrospective cohort study used the National Health Insurance Research Database in Taiwan to study KTRs (N = 4635), patients with end-stage renal disease (ESRD; N = 69,297), and patients from the general population who were chronic kidney disease (CKD)-free and matched by comorbidities (N = 69,297) for the years 2000 through 2010. The risk of stroke was analyzed using univariate and multivariate Cox regression models and compared between study cohorts. Findings: Compared with the ESRD subgroup, KTRs had a significantly lower risk of overall stroke (adjusted hazard ratio (aHR) = 0.37, 95% confidence interval (CI) = 0.31–0.44), ischemic stroke (aHR = 0.45, 95% CI = 0.37–0.55), and hemorrhagic stroke (aHR = 0.20, 95% CI = 0.14–0.29). The risk patterns for each type of stroke in the KTR group were not significantly different than those of the CKD-free control subgroup. The predictors of stroke were age and diabetes in KTRs. All forms of stroke after transplantation independently predicted an increased risk of subsequent mortality, and the strongest risk was related to hemorrhagic events. Interpretation: KTRs had a lower risk of stroke than ESRD patients, but this risk was not significantly different from that of the CKD-free comorbidities-matched general population group. Although stroke was relatively uncommon among cardiovascular events, it predicted unfavorable outcome in KTRs.

scholarly journals Which Kidney Transplant Recipients Can Benefit from the Initial Tacrolimus Dose Reduction?

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Kinga Krzyżowska ◽  
Aureliusz Kolonko ◽  
Piotr Giza ◽  
Jerzy Chudek ◽  
Andrzej Więcek
Keyword(s):  
Risk Factors ◽  
Dose Reduction ◽  
Kidney Transplant ◽  
Multiple Logistic Regression Analysis ◽  
Hemoglobin Concentration ◽  
Blood Levels ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Related Factors ◽  
Tacrolimus Dose

Background. Observational data suggest that the fixed initial recommended tacrolimus (Tc) dosing (0.2 mg/kg/day) results in supratherapeutic drug levels in some patients during the early posttransplant period. The aim of the study was to analyze a wide panel of patient-related factors and their interactions which increase the risk for first Tc blood level > 15 ng/ml. Materials and Methods. We performed a retrospective analysis of 488 consecutive adult kidney transplant recipients who were initially treated with triple immunosuppressive regimen containing tacrolimus twice daily. The analysis included the first assessment of Tc trough blood levels and several demographic, anthropometric, laboratory, and comedication data. Results. The multiple logistic regression analysis showed that age > 55 years, BMI > 24.6 kg/m2, blood hemoglobin concentration > 9.5 g/dl, and the presence of anti-HCV antibodies independently increased the risk for first Tc level > 15 ng/ml. The relative risk (RR) for first tacrolimus level > 15 ng/ml was 1.88 (95% CI 1.35–2.64, p<0.001) for patients with one risk factor and 2.81 (2.02–3.89, p<0.001) for patients with two risk factors. Conclusions. Initial tacrolimus dose reduction should be considered in older, overweight, or obese kidney transplant recipients and in subjects with anti-HCV antibodies. Moreover, dose reduction of tacrolimus is especially important in patients with coexisting multiple risk factors.

scholarly journals The NFKB1 Promoter Polymorphism (-94ins/delATTG) Is Associated with Susceptibility to Cytomegalovirus Infection after Kidney Transplantation and Should Have Implications on CMV Prophylaxis Regimens

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 380
Author(s):  
Hartmuth Nowak ◽  
Svenja Vornweg ◽  
Katharina Rump ◽  
Tim Rahmel ◽  
Matthias Unterberg ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Cox Regression ◽  
Opportunistic Infections ◽  
Late Onset ◽  
Association Studies ◽  
Promoter Polymorphism ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cmv Infection

Infections with cytomegalovirus (CMV) are one of the most frequent opportunistic infections in kidney transplant recipients. Current risk-adapted CMV chemoprophylaxis regimens are based almost solely on the donor and recipient CMV serostatus. Of note, the NFKB1 -94ins/delATTG promoter polymorphism was recently associated with a higher risk of CMV infection. Since single genetic association studies suffer from poor reliability for drawing therapeutic implications, we performed this confirmatory study and included 256 kidney transplant recipients from 2007 to 2014 in this retrospective study. Patients were genotyped for the -94ins/delATTG NFKB1 promoter polymorphism and followed up for 12 months. The incidence of CMV infection within 12 months after kidney transplantation was 37.5% (33/88) for the ins/ins, 21.5% (28/130) for the ins/del, and 23.7% (9/38) for the del/del genotypes (p = 0.023). Moreover, we evaluated the time of CMV infection onset. Ins/ins carriers had primarily late-onset CMV infection (median 194 days; interquartile range (IQR) 117–267 days) compared with heterozygous (ins/del; median 158 days; IQR 82–195 days) and homozygous deletion allele carriers (del/del; median 95 days; 84–123 days). Multivariate-restricted Cox regression model confirmed the ins/ins genotype to be an independent risk factor for the development of late-onset CMV infections. These findings should have an impact on post-kidney transplantation CMV chemoprophylaxis regimens.

scholarly journals 39. Anti-Spike Monoclonal Antibody Therapy for Kidney Transplant Recipients with COVID-19

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S28-S29
Author(s):  
Anna Hardesty ◽  
Elizabeth Klein ◽  
Kendra Vieira ◽  
Dimitrios Farmakiotis
Keyword(s):  
Kidney Transplant ◽  
Cox Regression ◽  
Organ Transplant ◽  
Passive Immunization ◽  
Time Dependent ◽  
Therapeutic Modality ◽  
Control Group ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Research Support

Abstract Background Organ transplant recipients may not mount an adequate immune response to COVID-19 infection, and therefore may benefit greatly from passive immunization with anti-spike monoclonal antibodies (mAb), which have been shown to decrease hospitalization rates in the general outpatient population. We evaluated the efficacy of mAb therapy in decreasing hospitalizations or emergency room (ER) visits among kidney transplant recipients (KTR) with COVID-19. Methods We identified KTR with COVID-19 between 3/1/2020 and 4/30/2021. Patients were excluded if they had multiorgan transplant or hospital-acquired COVID-19. Data were analyzed by Cox regression with mAb administration as time-dependent variable, and the day of symptom onset as baseline. Results We studied 95 KTR; 20 received mAb. Comorbidities and immunosuppression were balanced between the two groups. mAb administration was associated with a significant decrease in hospitalizations or ER visits (15 vs. 76%, P&lt; 0.001). This association remained significant after adjustment for confounders and by analyzing mAb administration as a time-dependent variable (Table: adj. HR 0.2, P=0.04). No KTR who received mAb died or required mechanical ventilation. Black or Hispanic KTR were less likely to receive mAb and more likely to be admitted to the hospital or visit the ER (Table). Table Factors significantly associated with hospitalization or ER visit. Conclusion In our KTR population, mAb therapy for COVID-19 may have helped decrease hospitalizations and ER visits. Healthcare inequities, including access to investigational treatments, were exacerbated by the COVID-19 pandemic. Acknowledging the nonconcurrent control group as a limitation, we found a strong signal for benefit from mAb treatment. Antiviral mAb are a promising therapeutic modality for immunosuppressed patients. Disclosures Dimitrios Farmakiotis, M.D., Astellas (Grant/Research Support)Merck (Grant/Research Support)Viracor (Grant/Research Support)

scholarly journals Androgens and Development of Posttransplantation Diabetes Mellitus in Male Kidney Transplant Recipients: A Post Hoc Analysis of a Prospective Study

2021 ◽  
Author(s):  
Suzanne P. Stam ◽  
Sara Sokooti ◽  
Michele F. Eisenga ◽  
Anna van der Veen ◽  
Antonio W. Gomes-Neto ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Transplant ◽  
Cox Regression ◽  
Continuous Variables ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
A Prospective Study ◽  
Post Hoc ◽  
Androgen Levels

<u>Objective.</u><b> </b>Post-transplantation Diabetes Mellitus (PTDM) effects up to 30% of all kidney transplant recipients (KTR). Recent studies in mice found that sufficient androgen levels are necessary for β-cell health and adequate insulin secretion. This raises the question whether a similar relationship might be present in KTR. Hence, we hypothesized that dihydrotestosterone and testosterone are associated with the development of PTDM in male KTR. <p><u>Research design and Methods.</u><b> </b>We conducted a post-hoc analyses of a prospective single-center cohort study including adult male KTR with a functioning graft ≥1 year post-transplantation. Androgen levels were assessed by liquid chromatography tandem mass spectrometry. Development of PTDM was defined according to the American Diabetes Association’s criteria. </p> <p><u>Results.</u><b> </b>We included 243 male KTR (age 51 ± 14 years), with a median dihydrotestosterone 0.9 [0.7–1.3] nmol/L and testosterone of 12.1 [9.4–15.8] nmol/L. During 5.3 [3.7–5.8] years of follow-up, 28 KTR (11.5%) developed PTDM. A clear association was observed as 15 (19%), 10 (12%), and 3 (4%) male KTR developed PTDM in the respective tertiles of dihydrotestosterone (P=0.008). In Cox regression analyses, both dihydrotestosterone and testosterone as continuous variables, were inversely associated with the risk to development PTDM, independent of glucose and HbA<sub>1c</sub> (HR 0.31; 95%CI[0.16–0.59], P<0.001 and HR 0.32; 95%CI[0.15–0.68], P=0.003 respectively). </p> <p><u>Conclusions.</u> Our results suggest that low androgen levels are a novel potential modifiable risk factor for the development of PTDM in male KTR. </p>

scholarly journals Long-term mortality among kidney transplant recipients with and without diabetes: a nationwide cohort study in the USA

2021 ◽  
Vol 9 (1) ◽  
pp. e001962
Author(s):  
Jessica L Harding ◽  
Meda Pavkov ◽  
Zhensheng Wang ◽  
Stephen Benoit ◽  
Nilka Ríos Burrows ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Cox Regression ◽  
Diabetes Type ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Risk Of Death ◽  
Effective Interventions ◽  
Diabetes Status ◽  
The Usa ◽  
End Stage

IntroductionLittle is known about the role diabetes (type 1 (T1D) and type 2 (T2D)) plays in modifying prognosis among kidney transplant recipients. Here, we compare mortality among transplant recipients with T1D, T2D and non-diabetes-related end-stage kidney disease (ESKD).Research design and methodsWe included 254 188 first-time single kidney transplant recipients aged ≥18 years from the US Renal Data System (2000–2018). Diabetes status, as primary cause of ESKD, was defined using International Classification of Disease 9th and 10th Clinical Modification codes. Multivariable-adjusted Cox regression models (right-censored) computed risk of death associated with T1D and T2D relative to non-diabetes. Trends in standardized mortality ratios (SMRs) (2000–2017), relative to the general US population, were assessed using Joinpoint regression.ResultsA total of 72 175 (28.4%) deaths occurred over a median survival time of 14.6 years. 5-year survival probabilities were 88%, 85% and 77% for non-diabetes, T1D and T2D, respectively. In adjusted models, mortality was highest for T1D (HR=1.95, (95% CI: 1.88 to 2.03)) and then T2D (1.65 (1.62 to 1.69)), as compared with non-diabetes. SMRs declined for non-diabetes, T1D, and T2D. However, in 2017, SMRs were 2.38 (2.31 to 2.45), 6.55 (6.07 to 7.06), and 3.82 (3.68 to 3.98), for non-diabetes, T1D and T2D, respectively.ConclusionsIn the USA, diabetes type is an important modifier in mortality risk among kidney transplant recipients with highest rates among people with T1D-related ESKD. Development of effective interventions that reduce excess mortality in transplant recipients with diabetes is needed, especially for T1D.

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