Prognostic value of hepatocyte growth factor for muscle-invasive bladder cancer

Abstract Purpose The HGF/MET pathway is involved in cell motility, angiogenesis, proliferation, and cancer invasion. We assessed the clinical utility of plasma HGF level as a prognostic biomarker in patients with MIBC. Methods We retrospectively analyzed 565 patients with MIBC who underwent radical cystectomy. Logistic regression and Cox regression models were used, and predictive accuracies were estimated using the area under the curve and concordance index. To estimate the clinical utility of HGF, DCA and MCID were applied. Results Plasma HGF level was significantly higher in patients with advanced pathologic stage and LN metastasis (p = 0.01 and p < 0.001, respectively). Higher HGF levels were associated with an increased risk of harboring LN metastasis and non-organ-confined disease (OR1.21, 95%CI 1.12–1.32, p < 0.001, and OR1.35, 95%CI 1.23–1.48, p < 0.001, respectively) on multivariable analyses; the addition of HGF improved the predictive accuracies of a standard preoperative model (+ 7%, p < 0.001 and + 8%, p < 0.001, respectively). According to the DCA and MCID, half of the patients had a net benefit by including HGF, but the absolute magnitude remained limited. In pre- and postoperative predictive models, a higher HGF level was significant prognosticator of worse RFS, OS, and CSS; in the preoperative model, the addition of HGF improved accuracies by 6% and 5% for RFS and CSS, respectively. Conclusion Preoperative HGF identified MIBC patients who harbored features of clinically and biologically aggressive disease. Plasma HGF could serve, as part of a panel, as a biomarker to aid in preoperative treatment planning regarding intensity of treatment in patients with clinical MIBC.

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Prognostic Value of Hepatocyte Growth Factor for Muscle-invasive Bladder Cancer

10.21203/rs.3.rs-931975/v1 ◽

2021 ◽

Author(s):

Satoshi Katayama ◽

Victor M. Schuettfort ◽

Benjamin Pradere ◽

Keiichiro Mori ◽

Hadi Mostafaei ◽

...

Keyword(s):

Clinical Utility ◽

Cox Regression ◽

Area Under The Curve ◽

Absolute Magnitude ◽

Preoperative Treatment ◽

Net Benefit ◽

Increased Risk ◽

Multivariable Analyses ◽

Muscle Invasive ◽

Hepatocyte Growth

Abstract PurposeThe HGF/MET pathway is involved in cell motility, angiogenesis, proliferation, and cancer invasion. We assessed the clinical utility of plasma HGF level as a prognostic biomarker in patients with MIBC.MethodsWe retrospectively analyzed 565 patients with MIBC who underwent radical cystectomy. Logistic regression and Cox regression models were used, and predictive accuracies were estimated using the area under the curve and concordance index. To estimate the clinical utility of HGF, DCA and MCID were applied.ResultsPlasma HGF level was significantly higher in patients with advanced pathologic stage and LN metastasis (p=0.01 and p<0.001, respectively). Higher HGF levels were associated with an increased risk of harboring LN metastasis and non-organ-confined disease (OR1.21, 95%CI 1.12-1.32, p<0.001, and OR1.35, 95%CI 1.23-1.48, p<0.001, respectively) on multivariable analyses; the addition of HGF improved the predictive accuracies of a standard preoperative model (+7%, p<0.001 and +8%, p<0.001, respectively). According to the DCA and MCID, half of the patients had a net benefit by including HGF, but the absolute magnitude remained limited. In pre- and postoperative predictive models, a higher HGF level was significant prognosticator of worse RFS, OS, and CSS; in the preoperative model, the addition of HGF improved accuracies by 6% and 5% for RFS and CSS, respectively.ConclusionPreoperative HGF identified MIBC patients who harbored features of clinically and biologically aggressive disease. Plasma HGF could serve, as part of a panel, as a biomarker to aid in preoperative treatment planning regarding intensity of treatment in patients with clinically MIBC.

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One-year outcomes in atrial fibrillation presenting during infections: a nationwide registry-based study

European Heart Journal ◽

10.1093/eurheartj/ehz873 ◽

2019 ◽

Vol 41 (10) ◽

pp. 1112-1119 ◽

Cited By ~ 4

Author(s):

Anna Gundlund ◽

Jonas Bjerring Olesen ◽

Jawad H Butt ◽

Mathias Aagaard Christensen ◽

Gunnar H Gislason ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cox Regression ◽

Absolute Risk ◽

First Year ◽

Thromboembolic Events ◽

Nationwide Registry ◽

Increased Risk ◽

Study Population ◽

Multivariable Analyses ◽

One Year

Abstract Aims Thromboprophylaxis guidelines for patients with concurrent atrial fibrillation (AF) during infections are unclear and not supported by data. We compared 1-year outcomes in patients with infection-related AF and infection without AF. Methods and results By crosslinking Danish nationwide registry data, AF naïve patients admitted with infection (1996–2016) were identified. Those with AF during the infection (infection-related AF) were matched 1:3 according to age, sex, type of infection, and year with patients with infection without AF. Outcomes (AF, thromboembolic events) were assessed by multivariable Cox regression. The study population comprised 30 307 patients with infection-related AF and 90 912 patients with infection without AF [median age 79 years (interquartile range 71–86), 47.6% males in both groups]. The 1-year absolute risk of AF and thromboembolic events were 36.4% and 7.6%, respectively (infection-related AF) and 1.9% and 4.4%, respectively (infection without AF). In the multivariable analyses, infection-related AF was associated with an increased long-term risk of AF and thromboembolic events compared with infection without AF: hazard ratio (HR) 25.98, 95% confidence interval (CI) 24.64–27.39 for AF and HR 2.10, 95% CI 1.98–2.22 for thromboembolic events. Further, differences in risks existed across different subtypes of infections. Conclusion During the first year after discharge, 36% of patients with infection-related AF had a new hospital contact with AF. Infection-related AF was associated with increased risk of thromboembolic events compared with infection without AF and our results suggest that AF related to infection may merit treatment and follow-up similar to that of AF not related to infection.

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Gemcitabine-cisplatin (GC) plus radical cystectomy-pelvic lymph node dissection (RC-PLND) for patients (pts) with muscle-invasive bladder cancer (MIBC): Assessing impacts of neoadjuvant chemotherapy (NAC) and the PLND.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.355 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 355-355 ◽

Cited By ~ 6

Author(s):

Christopher Michael Tully ◽

Bernard H. Bochner ◽

Guido Dalbagni ◽

Emily C. Zabor ◽

Harry W. Herr ◽

...

Keyword(s):

Cox Regression ◽

Clinical Stage ◽

Univariate Analysis ◽

Disease Free Survival ◽

Dose Intensity ◽

Complete Response ◽

Risk Of Death ◽

Increased Risk ◽

Muscle Invasive ◽

The Individual

355 Background: NAC and RC-PLND improves survival in MIBC and GC is a standard NAC option. However, little is known about GC efficacy endpoints and the individual contribution of NAC and surgery. Methods: Pts with clinical T2-T4aN0M0 MIBC treated from 1/2000 to 10/2012 with a planned 4 cycles of GC plus RC-PLND within 90 days (D) of NAC were evaluated retrospectively for the number (#) of cycles, dose delivered, D from end of NAC to RC-PLND, margin status, LN status and # of LN identified. Post-NAC pathologic endpoints included complete response (pT0), residual Non-MIBC disease (pTa/Tis/T1;N0) and ≥MIBC disease (≥pT2N0). Associations with overall survival (OS) and disease-free survival were analyzed using Cox regression; non-linear associations with # of resected LN used linear and quadratic terms. Results: 154 pts met inclusion criteria. 5-year (yr) OS was 61% (95% CI 53-71%). Post-NAC pT0 was achieved in 21% (32/154) and Non-MIBC in 25% (39/154 - pTa (2), pTis (25), pT1 (12)). Post-NAC pT0 and Non-MIBC had similar 5-yr OS (85% and 89%, respectively) and combined (<pT2) pts differed significantly from pts with ≥pT2, (87% (95% CI 78, 98%) and 38% (95% CI 27, 53%), respectively; p<0.001). Median D from NAC to RC-PLND was 34 and median # of resected LN was 19. On univariate analysis, # of cycles (4 vs <4), GC dose intensity and total dose, clinical stage (cT2 vs cT3/cT4), # of resected LN, positive (+) LN and + margins were significant for OS. In multivariate analysis, post-NAC pathology ≥pT2 (HR 6.7; 95% CI 2.6-17.4; p<0.001), + LN (HR 3.21; 95% CI 1.6-6.4; p=0.001) and + margins (HR 3.2; 95% CI 1.4-7.5; p=0.007) were significant for increased risk of death. Using a model with these 3 predictors to estimate the benefit of PLND, the hazard ratio decreased with each LN resected until 25 and then plateaued beyond 25 (p=0.016). Conclusions: NAC with GC has excellent drug delivery, permits rapid RC-PLND and achieves meaningful pathologic responses. Survival is similar with <pT2N0 and pT0N0 post NAC pathology. Pts with post NAC ≥pT2, + margins, and + LN do poorly. Increasing LN yield on PLND contributes to OS.

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Impact of obesity on survival in patients (pts) with early-stage squamous cell carcinoma (SCC) of the oral tongue.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.6048 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 6048-6048

Author(s):

Neil M. Iyengar ◽

Amit Kochhar ◽

Patrick Glyn Morris ◽

Luc G. Morris ◽

Xi Kathy Zhou ◽

...

Keyword(s):

Cox Regression ◽

Nutritional Assessment ◽

Tongue Cancer ◽

Early Stage ◽

Oral Tongue ◽

Clinicopathologic Characteristics ◽

Prognostic Effect ◽

Increased Risk ◽

Secondary Endpoints ◽

Multivariable Analyses

6048 Background: Obesity is a risk factor for several malignancies and an independent predictor of worse outcomes. In contrast, low body mass index (BMI) has been associated with increased risk of oropharyngeal cancers and poorer prognosis. In tongue SCC, impaired nutrition, smoking, and alcohol use impact BMI, and pre-diagnosis weight (wgt) loss negatively affects survival. The prognostic effect of obesity in tongue cancer is unknown. Methods: We conducted a single-institution, retrospective study of pts who underwent resection of T1/T2 SCC of the oral tongue. All pts underwent nutritional assessment prior to surgery. BMI was calculated from measured height and wgt at surgery and categorized as obese (≥30), overwgt (25-29.9), or normal (18.5-24.9). The association between BMI and the primary endpoint, disease specific survival (DSS), was evaluated by Cox regression. The effect of BMI on the secondary endpoints, recurrence free survival (RFS) and overall survival (OS), was also assessed. Results: From 2000 to 2005, 155 pts (90 men, 65 women) of median age 57 (range 18-86) were included. Clinicopathologic characteristics were similar by BMI group. Obesity was significantly associated with adverse DSS compared with normal wgt in univariable (Table) and multivariable analyses (HR 2.87; 95% CI, 1.08-7.67; p=0.04). Obesity was also significantly associated with adverse RFS (HR 2.53; 95% CI, 1.12-5.74; p=0.03). Overwgt subjects may also have worse RFS (HR 1.74; 95% CI, 0.85-3.55; p=0.13). In pts without pre-diagnosis wgt loss (n=94), obesity was significantly associated with adverse OS (HR 2.70; 95% CI, 1.12-6.54; p=0.03). Conclusions: These data suggest that obesity is associated with a worse prognosis in tongue cancer, which may not have previously been appreciated due to confounding by pre-diagnosis wgt loss. [Table: see text]

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MO589PLASMA CONCENTRATIONS OF TRIMETHYLAMINE N-OXIDE, AND ITS DIETARY DETERMINANTS ARE ASSOCIATED WITH INCREASED RISK OF GRAFT FAILURE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab089.002 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Jose L Flores-Guerrero ◽

Maryse C.J. Osté ◽

Paula B Baraldi ◽

Margery A Connelly ◽

Erwin Garcia ◽

...

Keyword(s):

Prediction Model ◽

Graft Failure ◽

Clinical Utility ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Renal Transplant Recipients ◽

Net Benefit ◽

Increased Risk ◽

Modifiable Factors ◽

Multivariable Regression

Abstract Background and Aims Due to the critical shortage of kidneys for transplantation, the identification of modifiable factors related to graft failure is highly desirable. The role of trimethylamine-N-oxide (TMAO) in graft failure remains undetermined. Here we aimed to investigate the clinical utility of TMAO and its dietary determinants for graft failure prediction in renal transplant recipients (RTRs). Method We included 448 RTRs who participated in the TransplantLines Cohort Study. Cox proportional-hazards regression analyses were performed to study the association of plasma TMAO with graft failure. Net Benefit, a decision analysis method, was performed to evaluate the clinical utility of TMAO and dietary information in the prediction of graft failure. Results Among RTRs (age 52.7 ± 13.1 years; 53% males), baseline median TMAO was 5.6 (3.0–10.2) µmol/L. In multivariable regression analysis, the most important dietary determinants of TMAO were egg intake (Std. β = 0.10 [95%CI, 0.01;0.19]; P=0.03), fiber intake (Std. β = -0.13 [95%CI, -0.22, -0.05]; P =0.002), and fish and seafood intake (Std. β = 0.11 [95%CI, 0.02,0.20]; P=0.01). After a median follow-up of 5.3 (4.5–6.0) years, graft failure was observed in 58 subjects. TMAO was associated with increased risk of graft failure, independent of age, sex, BMI, blood pressure, lipids, albuminuria and eGFR (Hazard Ratio per 1-SD increase of TMAO, 1.62 (95% confidence interval (CI): 1.22; 2.14, P<0.001). A TMAO and dietary enhanced prediction model offered approximately double Net Benefit compared to a previously reported, validated prediction model for future graft failure, allowing the detection of 21 RTRs per 100 RTRs tested with no false positives versus 10 RTRs respectively. Conclusion A predictive model for graft failure, enriched with TMAO and its dietary determinants yielded a higher Net Benefit compared with an already validated model. This study suggests that TMAO and its dietary determinants are associated with an increased risk of graft failure and that it is clinically meaningful.

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Abstract P143: Circulating Level of Hepatocyte Growth Factor and Incidence of Diabetes Mellitus: The Multi-Ethnic Study of Atherosclerosis

Circulation ◽

10.1161/circ.131.suppl_1.p143 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Michael P Bancks ◽

Suzette J Bielinski ◽

Paul A Decker ◽

Naomi Q Hanson ◽

Nicholas B Larson ◽

...

Keyword(s):

Growth Factor ◽

Hepatocyte Growth Factor ◽

Cox Regression ◽

Fasting Glucose ◽

Smoking Status ◽

Incident Diabetes ◽

Hazard Ratios ◽

Increased Risk ◽

Race Ethnicity ◽

Hepatocyte Growth

Introduction: Increased levels of hepatocyte growth factor (HGF), active in cell growth, motility, and morphogenesis, are associated with the presence of obesity, poor metabolic health, and cardiovascular disease. Hypothesis: We assessed the hypothesis that higher baseline levels of HGF will be associated with increased risk of diabetes. Methods: We examined the association between HGF and incident diabetes in MESA, including 5395 men and women 45-84 years of age at enrollment (2000-02). Fasting serum HGF was measured at baseline and on a subsample of participants at exam 2 (n = 1915). From 2000-11, incidence of diabetes was ascertained over 4 follow-up examinations, determined by new use of insulin or oral hypoglycemic medication or fasting glucose ≥ 126 mg/dL. Cox regression was used to estimate hazard ratios (HR) for incident diabetes according to 1 standard deviation unit (SDU) of HGF (1 SDU =256 pg/mL), before and after adjustment for age, sex, race/ethnicity, education, study center, smoking status, alcohol consumption, BMI, WC, fasting glucose and insulin, CRP, and IL-6 levels. Similarly, hazard ratios for incident diabetes were estimated according to change in HGF levels from exam 1 to exam 2 in the subsample. Results: At baseline, older age, male sex, current smoking, and higher body mass index (BMI), waist circumference (WC), fasting glucose and insulin, C-reactive protein (CRP) and interleukin-6 (IL-6) levels were all associated with higher levels of HGF, while greater education and physical activity were associated with lower serum HGF. Incidence of diabetes in this analytic sample was 12% (n cases = 670). Per 1 SDU increase in baseline HGF level, unadjusted risk for diabetes increased 1.46 fold (95% CI=1.37, 1.56). After adjustment, diabetes risk per 1 SDU increase in HGF was attenuated but remained significantly increased (HR=1.22; 95% CI=1.12, 1.32). No association was found between change in HGF level between exam 1 and exam 2 and incidence of diabetes. There was no evidence of effect modification by race/ethnicity for either analysis. Conclusion: In conclusion, in this ethnically diverse U.S. adult population, higher levels of serum HGF were independently associated with increased incidence of diabetes.

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Hyperuricemia as a prognostic marker for long-term outcomes in patients with myocardial infarction with nonobstructive coronary arteries

Nutrition & Metabolism ◽

10.1186/s12986-021-00636-2 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Wenjian Ma ◽

Side Gao ◽

Sizhuang Huang ◽

Jiansong Yuan ◽

Mengyue Yu

Keyword(s):

Myocardial Infarction ◽

Coronary Arteries ◽

Cox Regression ◽

Serum Uric Acid Level ◽

Area Under The Curve ◽

Study Endpoint ◽

Major Adverse Cardiovascular Events ◽

Primary Study ◽

Propensity Score Matching Analysis ◽

Increased Risk

Abstract Background Hyperuricemia (HUA) has been proved as a predictor of worse outcomes in patients with coronary artery disease. Here, we investigated the prognostic value of HUA in a distinct population with myocardial infarction with nonobstructive coronary arteries (MINOCA). Methods A total of 1179 MINOCA patients were enrolled and divided into HUA and non-HUA groups. HUA was defined as a serum uric acid level ≥ 420 μmol/L in men or ≥ 357 μmol/L in women. The primary study endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, nonfatal stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan–Meier, Cox regression, and receiver-operating characteristic analyses were performed. Results Patients with HUA (prevalence of 23.5%) had a significantly higher incidence of MACE (18.7% vs. 12.8%; p = 0.015) than patients without during the median follow-up of 41.7 months. HUA was closely associated with an increased risk of MACE even after multivariable adjustment (hazard ratio 1.498, 95% confidence interval: 1.080 to 2.077; p = 0.016). HUA remained a robust risk factor of MACE after propensity score matching analysis. Moreover, HUA showed an area under the curve (AUC) of 0.59 for predicting MACE. Incorporation of HUA to the thrombolysis in myocardial infarction (TIMI) score yielded a significant improvement in discrimination for MACE. Conclusions HUA was independently associated with poor prognosis after MINOCA. Routine assessment of HUA may facilitate risk stratification in this specific population.

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MO503SAFETY AND EFFICACY OF ANTICOAGULATION IN PATIENTS WITH EGFR<30 ML/MIN/1.73 M2 AND ATRIAL FIBRILLATION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab087.0023 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Ellen Linnea Freese Ballegaard ◽

Jonas Bjerring Olesen ◽

Anne Lise Kamper ◽

Bo Feldt-Rasmussen ◽

Gunnar Gislason ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Cox Regression ◽

De Novo ◽

Anticoagulation Therapy ◽

Net Benefit ◽

Dialysis Therapy ◽

Risk Of Bleeding ◽

Increased Risk ◽

One Year

Abstract Background and Aims Net benefit of anticoagulation in patients with eGFR <30 ml/min/1.73 m2 and atrial fibrillation remains uncertain. The aim of this study was to evaluate the use, efficacy and safety of anticoagulation therapy in patients with eGFR<30 ml/min/1.73m2 (including dialysis treated patients) and atrial fibrillation. Method In a retrospective cohort study, all patients with atrial fibrillation and eGFR<30 ml/min/1.73 m2 were identified in nationwide Danish registers between 2008 and 2018. Cumulative incidences of stroke and major bleeding stratified on anticoagulation treatment were computed using the Aalen-Johansen estimator. One-year risks of stroke and major bleeding were calculated with comparison of treatment vs. no treatment based on Cox regression models adjusted for age, sex and dialysis status with G-computation of one-year risks standardized to the distribution of risk factors in the sample. Major bleeding was defined as any diagnosis of bleeding leading to hospitalization. Results A total of 2,452 patients with eGFR <30 ml/min/1.73 m2 and de novo atrial fibrillation were identified. Mean age was 78.8 years, 51.3% were male and 20% received dialysis therapy. Anticoagulation therapy was initiated in 877 patients (35.8%), with warfarin accounting for 58.6% of all prescriptions. Overall, one-year standardized risk of bleeding was 10.6% (95% confidence interval (CI) 8.7%-12.7%) and 8.2% (95% CI 6.9%-9.5%) in patients with and without anticoagulation, while the risks of stroke were 3.6% (95% CI 2.6%-4.5%) and 5.1% (95% CI 4.1%-6.1%), respectively. In subgroup analyses of patients dependent vs. non-dependent on dialysis, the standardized one-year risk of bleeding was 13.3% (95% CI 9.0%-19.8%) vs. 10.4% (95% CI 8.6%-12.4%) in patients with anticoagulation and 9.0% (95% CI 6.5%-12.0%) vs. 7.8% (95% CI 6.5%-9.2%) in patients without anticoagulation. While the risk of stroke was 3.5% (95% CI 0.8%-6.7%) vs. 3.5% (95% CI 2.5%-4.9%) in patients with anticoagulation and 5.7% (95% CI 3.5%-7.8%) vs. 4.9% (95% CI 3.7% vs. 6.3%) in patients without anticoagulation. Cumulative incidences of major bleeding and stroke are shown in the figure. Conclusion Use of anticoagulation was associated with increased risk of bleeding and reduced risk of stroke in patients with eGFR<30 ml/min/1.73 m2 and atrial fibrillation. Randomized controlled trials are needed to establish the benefit and harm of anticoagulation in this population.

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Prediction of Recurrence Patterns in Glioblastoma Using DSC-MRI Radiomics-Based Deep Learning

10.21203/rs.3.rs-125593/v1 ◽

2020 ◽

Author(s):

Ka Young Shim ◽

Sung Won Chung ◽

Jae Hak Jeong ◽

Inpyeong Hwang ◽

Chul-Kee Park ◽

...

Keyword(s):

Deep Learning ◽

Local Recurrence ◽

Cox Regression ◽

Area Under The Curve ◽

Progression Free Survival ◽

Distant Recurrence ◽

High Rate ◽

Neural Network Models ◽

Increased Risk ◽

Recurrence Patterns

Abstract Glioblastoma remains the most devastating brain tumor despite optimal treatment, because of the high rate of recurrence. Distant recurrence has distinct genomic alterations compared to local recurrence, which requires different treatment planning both in clinical practice and trials. To date, perfusion-weighted MRI has revealed that perfusional characteristics of tumor are associated with prognosis. However, not much research has focused on recurrence patterns in glioblastoma: namely, local and distant recurrence. Here, we propose two different neural network models to predict the recurrence patterns in glioblastoma that utilizes high-dimensional radiomic profiles based on perfusion MRI: area under the curve (AUC) (95% confidence interval), 0.969 (0.903-1.000) for local recurrence; 0.864 (0.726-0.976) for distant recurrence for each patient in the validation set. This creates an opportunity to provide personalized medicine in contrast to studies investigating only group differences. Moreover, interpretable deep learning identified that salient radiomic features for each recurrence pattern are related to perfusional intratumoral heterogeneity. We also demonstrated that the combined salient radiomic features, or “radiomic risk score”, increased risk of recurrence/progression (hazard ratio, 1.61; p=0.03) in multivariate Cox regression on progression-free survival.

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Association of Circulating Trimethylamine N-Oxide and Its Dietary Determinants with the Risk of Kidney Graft Failure: Results of the TransplantLines Cohort Study

Nutrients ◽

10.3390/nu13010262 ◽

2021 ◽

Vol 13 (1) ◽

pp. 262

Author(s):

Jose L. Flores-Guerrero ◽

Maryse C. J. Osté ◽

Paula B. Baraldi ◽

Margery A. Connelly ◽

Erwin Garcia ◽

...

Keyword(s):

Cohort Study ◽

Prediction Model ◽

Graft Failure ◽

Clinical Utility ◽

The Body ◽

Renal Transplant Recipients ◽

Kidney Graft ◽

Net Benefit ◽

Increased Risk ◽

Modifiable Factors

Background. Due to the critical shortage of kidneys for transplantation, the identification of modifiable factors related to graft failure is highly desirable. The role of trimethylamine-N-oxide (TMAO) in graft failure remains undetermined. Here, we investigated the clinical utility of TMAO and its dietary determinants for graft failure prediction in renal transplant recipients (RTRs). Methods. We included 448 RTRs who participated in the TransplantLines Cohort Study. Cox proportional-hazards regression analyses were performed to study the association of plasma TMAO with graft failure. Net Benefit, which is a decision analysis method, was performed to evaluate the clinical utility of TMAO and dietary information in the prediction of graft failure. Results. Among RTRs (age 52.7 ± 13.1 years; 53% males), the baseline median TMAO was 5.6 (3.0–10.2) µmol/L. In multivariable regression analysis, the most important dietary determinants of TMAO were egg intake (Std. β = 0.09 [95%CI, 0.01; 0.18]; p = 0.03), fiber intake (Std. β = −0.14 [95%CI, −0.22, −0.05]; p = 0.002), and fish and seafood intake (Std. β = 0.12 [95%CI, 0.03,0.21]; p = 0.01). After a median follow-up of 5.3 (4.5–6.0) years, graft failure was observed in 58 subjects. TMAO was associated with an increased risk of graft failure, independent of age, sex, the body mass index (BMI), blood pressure, lipids, albuminuria, and the Estimated Glomerular Filtration Rate (eGFR) (Hazard Ratio per 1-SD increase of TMAO, 1.62 (95% confidence interval (CI): 1.22; 2.14, p < 0.001)). A TMAO and dietary enhanced prediction model offered approximately double the Net Benefit compared to a previously reported, validated prediction model for future graft failure, allowing the detection of 21 RTRs per 100 RTRs tested, with no false positives versus 10 RTRs, respectively. Conclusions. A predictive model for graft failure, enriched with TMAO and its dietary determinants, yielded a higher Net Benefit compared with an already validated model. This study suggests that TMAO and its dietary determinants are associated with an increased risk of graft failure and that it is clinically meaningful.

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