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 ◽  
...  

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.

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Chang Chu ◽  
Saban Elitok ◽  
Shufei Zeng ◽  
Yingquan Xiong ◽  
Carl-Friedrich Hocher ◽  
...  

Abstract Background Increased fibroblast growth factor 23 (FGF23) is a risk factor for mortality, cardiovascular disease, and progression of chronic kidney disease. Limited data exist comparing the association of either c-terminal FGF23 (cFGF23) or intact FGF23 (iFGF23) in kidney transplant recipients (KTRs) with overall (all-cause) graft loss. Methods We conducted a prospective observational cohort study in 562 stable kidney transplant recipients. Patients were followed for graft loss and all-cause mortality for a median follow-up of 48 months. Results During a median follow-up of 48 months, 94 patients had overall graft loss (primary graft loss or death with functioning graft). Both cFGF23 and iFGF23 concentrations were significantly higher in patients with overall graft loss than those without (24.59 [11.43–87.82] versus 10.67 [5.99–22.73] pg/ml; p < 0.0001 and 45.24 [18.63–159.00] versus 29.04 [15.23–60.65] pg/ml; p = 0.002 for cFGF23 and iFGF23, respectively). Time-dependent ROC analysis showed that cFGF23 concentrations had a better discriminatory ability than iFGF23 concentrations in predicting overall (all-cause) graft loss. Cox regression analyses adjusted for risk factors showed that cFGF23 (HR for one unit increase of log transformed cFGF23: 1.35; 95% CI, 1.01–1.79; p = 0.043) but not iFGF23 (HR for one unit increase of log transformed iFGF23: 0.97; 95% CI, 0.75–1.25; p = 0.794) was associated with the overall graft loss. Conclusion Elevated cFGF23 concentrations at baseline are independently associated with an increased risk of overall graft loss. iFGF23 measurements were not independently associated with overall graft loss. The cFGF23 ELISA might detect bioactive FGF23 fragments that are not detected by the iFGF23 ELISA.


2014 ◽  
Vol 97 (9) ◽  
pp. 925-933 ◽  
Author(s):  
Jeffrey J. Gaynor ◽  
Gaetano Ciancio ◽  
Giselle Guerra ◽  
Junichiro Sageshima ◽  
Lois Hanson ◽  
...  

2017 ◽  
Vol 46 (4) ◽  
pp. 343-354 ◽  
Author(s):  
Ngan N. Lam ◽  
Amit X. Garg ◽  
Greg A. Knoll ◽  
S. Joseph Kim ◽  
Krista L. Lentine ◽  
...  

Background: The implications of venous thromboembolism (VTE) for morbidity and mortality in kidney transplant recipients are not well described. Methods: We conducted a retrospective study using linked healthcare databases in Ontario, Canada to determine the risk and complications of VTE in kidney transplant recipients from 2003 to 2013. We compared the incidence rate of VTE in recipients (n = 4,343) and a matched (1:4) sample of the general population (n = 17,372). For recipients with evidence of a VTE posttransplant, we compared adverse clinical outcomes (death, graft loss) to matched (1:2) recipients without evidence of a VTE posttransplant. Results: During a median follow-up of 5.2 years, 388 (8.9%) recipients developed a VTE compared to 254 (1.5%) in the matched general population (16.3 vs. 2.4 events per 1,000 person-years; hazard ratio [HR] 7.1, 95% CI 6.0-8.4; p < 0.0001). Recipients who experienced a posttransplant VTE had a higher risk of death (28.5 vs. 11.2%; HR 4.1, 95% CI 2.9-5.8; p < 0.0001) and death-censored graft loss (13.1 vs. 7.5%; HR 2.3, 95% CI 1.4-3.6; p = 0.0006) compared to matched recipients who did not experience a posttransplant VTE. Conclusions: Kidney transplant recipients have a sevenfold higher risk of VTE compared to the general population with VTE conferring an increased risk of death and graft loss.


2020 ◽  
Vol 31 (6) ◽  
pp. 1150-1156 ◽  
Author(s):  

BackgroundThe novel SARS-CoV-2 virus has caused a global pandemic of coronavirus disease 2019 (COVID-19). Although immunosuppressed individuals are thought to be at an increased risk of severe disease, little is known about their clinical presentation, disease course, or outcomes.MethodsWe report 15 kidney transplant recipients from the Columbia University kidney transplant program who required hospitalization for confirmed COVID-19, and describe their management, clinical course, and outcomes.ResultsPatients presented most often with a fever (87%) and/or cough (67%). Initial chest x-ray most commonly showed bilateral infiltrates, but 33% had no acute radiographic findings. Patients were managed with immunosuppression reduction and the addition of hydroxychloroquine and azithromycin. Although 27% of our patients needed mechanical ventilation, over half were discharged home by the end of follow-up.ConclusionsKidney transplant recipients with COVID-19 have presentations that are similar to that of the general population. Our current treatment protocol appears to be associated with favorable outcomes, but longer follow-up of a larger cohort of patients is needed.


Author(s):  
Shih-Ting Huang ◽  
Tung-Min Yu ◽  
Ya-Wen Chuang ◽  
Mu-Chi Chung ◽  
Chen-Yu Wang ◽  
...  

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.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Stanley Ming Hol Yeung ◽  
António W Gomes-Neto ◽  
Maryse C.J. Osté ◽  
Else Van den Berg ◽  
Jenny E Kootstra-Ros ◽  
...  

Abstract Background and Aims Dietary acid load is associated with low grade metabolic acidosis and might accelerate kidney function decline in patients with chronic kidney disease (CKD). We investigated whether dietary acid load, estimated as net endogenous acid production (NEAP), is associated with kidney function decline in kidney transplant recipients (KTR) and to what extent this association is mediated by variation in venous bicarbonate (HCO3-). Method We used data from 642 KTR with a functioning graft ≥1 year after transplantation who were enrolled in the Transplantlines Food & Nutrition Cohort Study between 2008-2011. We applied the Frassetto equation (NEAP = (54.5 X protein (g/d) / potassium (mEq/d) - 10.2)) to calculate NEAPFFQ using intake reported in food frequency questionnaires and NEAPUrine from assessments of 24 hours urinary urea and potassium excretion. Patients were divided into tertiles of NEAP and differences across tertiles were analyzed by ANOVA, Kruskall-Wallis and Chi-Square tests, as appropriate. Cox regression models were used to study the associations between NEAPFFQ and NEAPUrine (both continuous variables and categories) with the composite endpoint kidney function decline, defined as doubling of serum creatinine or graft failure. Mediation analyses were performed to evaluate whether these associations were explained by venous bicarbonate. Results Mean age was 53±13 years, 56.1% were men, and mean eGFR was 52±20 ml/min/1.73m2. Patients within the highest tertile of NEAPFFQ were younger (P=0.04), more recently transplanted (P=0.002), consumed less fruit and vegetables (P&lt;0.001), more fish (P=0.001), less alcohol (P=0.01), more meat (P&lt;0.001) and had lower serum HCO3- concentration (P=0.02). During a median follow-up time of 5.3 (4.1-6.0) years, 121 (18.8%) patients developed kidney function decline. In multivariable Cox regression analysis, higher NEAPFFQ (per SD increase) was associated with increased risk of kidney function decline, independent of potential confounders, including age, sex, BMI, time after transplantation, primary kidney disease, eGFR and proteinuria (adjusted HR 1.30; 95%CI 1.10-1.53, P=0.002). Compared to patients in the lowest NEAPFFQ tertile, those in the highest tertile had a &gt;1.5 higher risk of kidney function decline (adjusted HR 1.67; 95%CI 1.07-2.62, P=0.03). We observed similar results using NEAPUrine as the study exposure (adjusted HR 1.46 per SD increase; 95%CI 1.24-1.73, P&lt;0.001; adjusted HR 1.99; 95%CI 1.24-3.18, P=0.004 for patients in the highest versus lowest tertile of NEAPUrine). These associations between NEAPFFQ (Figure A) and NEAPUrine (Figure B) with kidney function decline were visualized by fitting multivariable Cox regression models based on restricted cubic splines. Mediation analyses estimated that venous HCO3- at baseline mediated 19.3% (P=0.008) of the association between NEAPFFQ and kidney function decline and 26.5% (P=0.002) of the association between NEAPUrine with kidney function decline. Conclusion Higher NEAP is associated with a higher risk for kidney function decline in KTR, and this association was in part mediated by venous HCO3-. We speculate that reducing dietary acid load might mitigate the risk of kidney function decline in KTR.


2008 ◽  
Vol 85 (3) ◽  
pp. 344-352 ◽  
Author(s):  
Luca Neri ◽  
Lisa A. Rocca Rey ◽  
Brett W. Pinsky ◽  
Krista L. Lentine ◽  
Paolo R. Salvalaggio ◽  
...  

2019 ◽  
Vol 35 (4) ◽  
pp. 706-714 ◽  
Author(s):  
Adriana J van Ballegooijen ◽  
Joline W J Beulens ◽  
Charlotte A Keyzer ◽  
Gerjan J Navis ◽  
Stefan P Berger ◽  
...  

Abstract Background Kidney transplant recipients (KTRs) experience substantial survival benefit compared with dialysis patients. However, their mortality and graft failure risk remain high. KTRs are often low in micronutrient status, including vitamins D and K. We investigated the association of both vitamins D and K status, and vitamin D treatment with all-cause mortality and death-censored graft failure. Methods We studied 461 KTRs from a single-centre study at median 6.1 years after transplantation. At baseline, vitamins D and K concentrations were measured by 25-hydroxyvitamin D [25(OH)D] and dephosphorylated uncarboxylated matrix gla protein (dp-ucMGP) and patients were categorized into: 25(OH)D &lt;50/≥50 nmol/L and median dp-ucMGP &lt;1057/≥1057 pmol/L. Results Mean age was 52 ± 12 years, and 122 KTRs (26%) had low vitamins D and K status. During median 9.8 years follow-up, 128 patients (28%) died and 48 (10%) developed death-censored graft failure. Low vitamins D and K status was associated with 2.33 (1.26–4.30) [hazard ratio (95% confidence interval)] increased mortality risk and 3.25 (1.17–9.08) increased graft failure risk compared with KTR with 25(OH)D ≥50 nmol/L and dp-ucMGP &lt;1057 pmol/L. Dp-ucMGP was strongly associated with mortality (per 500 pmol/L increase): 1.41 (1.08–1.41) for vitamin D treatment versus no treatment 1.07 (0.97–1.18), and graft failure 1.71 (1.17–2.49) for vitamin D treatment versus 1.19 (1.05–1.36) no treatment, P-interaction &lt;0.07 for vitamin D treatment (n = 44). Conclusions Combined vitamins D and K deficiency are highly prevalent and are associated with increased mortality and graft failure risk compared with high vitamins D and K status. Low vitamin K status was strongly associated with an increased risk of premature mortality and graft failure for patients treated with vitamin D versus no vitamin D treatment.


2020 ◽  
Vol 9 (2) ◽  
pp. 417 ◽  
Author(s):  
Camilo G. Sotomayor ◽  
Dion Groothof ◽  
Joppe J. Vodegel ◽  
Tomás A. Gacitúa ◽  
António W. Gomes-Neto ◽  
...  

Arsenic is toxic to many organ systems, the kidney being the most sensitive target organ. We aimed to investigate whether, in kidney transplant recipients (KTRs), the nephrotoxic exposure to arsenic could represent an overlooked hazard for graft survival. We performed a prospective cohort study of 665 KTRs with a functional graft ≥1 year, recruited in a university setting (2008‒2011), in The Netherlands. Plasma arsenic was measured by ICP-MS, and dietary intake was comprehensively assessed using a validated 177-item food-frequency questionnaire. The endpoint graft failure was defined as restart of dialysis or re-transplantation. Median arsenic concentration was 1.26 (IQR, 1.04‒2.04) µg/L. In backwards linear regression analyses we found that fish consumption (std β = 0.26; p < 0.001) was the major independent determinant of plasma arsenic. During 5 years of follow-up, 72 KTRs developed graft failure. In Cox proportional-hazards regression analyses, we found that arsenic was associated with increased risk of graft failure (HR 1.80; 95% CI 1.28–2.53; p = 0.001). This association remained materially unaltered after adjustment for donor and recipient characteristics, immunosuppressive therapy, eGFR, primary renal disease, and proteinuria. In conclusion, in KTRs, plasma arsenic is independently associated with increased risk of late graft failure.


2020 ◽  
Vol 5 (3) ◽  
pp. S328
Author(s):  
C.G. SOTOMAYOR ◽  
J.J. Vodegel ◽  
D. Groothof ◽  
M.F. Eisenga ◽  
T.J. Knobbe ◽  
...  

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