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Plasma Vitamin C and Risk of Late Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Biobank and Cohort Study.

ABSTRACT: Recent studies have shown that depletion of vitamin C is frequent in outpatient kidney transplant recipients (KTR) and that vitamin C is inversely associated with risk of death. Whether plasma vitamin C is associated with death-censored kidney graft failure remains unknown. We investigated KTR who participated in the TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study. The primary outcome was graft failure (restart of dialysis or re-transplantation). Overall and stratified (p_interaction < 0.1) multivariable-adjusted Cox regression analyses are presented here. Among 598 KTR (age 51 ± 12 years-old; 55% males), baseline median (IQR) plasma vitamin C was 44.0 (31.0-55.3) µmol/L. Through a median follow-up of 9.5 (IQR, 6.3‒10.2) years, 75 KTR developed graft failure (34, 26, and 15 events over increasing tertiles of vitamin C, log-rank p < 0.001). Plasma vitamin C was inversely associated with risk of graft failure (HR per 1-SD increment, 0.69; 95% CI 0.54-0.89; p = 0.004), particularly among KTR with triglycerides ≥1.9 mmol/L (HR 0.46; 95% CI 0.30-0.70; p < 0.001; p_interaction = 0.01) and among KTR with HDL cholesterol ≥0.91 mmol/L (HR 0.56; 95% CI 0.38-0.84; p = 0.01; p_interaction = 0.04). These findings remained materially unchanged in multivariable-adjusted analyses (donor, recipient, and transplant characteristics, including estimated glomerular filtration rate and proteinuria), were consistent in categorical analyses according to tertiles of plasma vitamin C, and robust after exclusion of outliers. Plasma vitamin C in outpatient KTR is inversely associated with risk of late graft failure. Whether plasma vitamin C‒targeted therapeutic strategies represent novel opportunities to ease important burden of graft failure necessitates further studies.

SUBMITTER: Sotomayor CG

PROVIDER: S-EPMC8143099 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundNeurocognitive impairment is common in kidney transplant recipients (KTRs). Adequate brain functioning requires energy and neurotransmitter activity, for which iron is essential. We aimed to investigate iron deficiency (ID) as a potentially modifiable risk factor for cognitive impairment in KTRs.MethodsWe analyzed stable KTRs participating in the TransplantLines Biobank and Cohort study. Participants underwent neuropsychological tests for memory, mental speed, and attention and executive functioning. ID was defined as ferritin <100 µg/mL or 100-299 µg/mL with transferrin saturation (TSAT) ≤20%. Associations between iron status and norm scores of neurocognitive outcomes, corrected for age, sex and education, were assessed using multivariable linear regression analyses adjusted for potential confounders including hemoglobin.ResultsWe included 166 KTRs [median (IQR) age 57 (45-65) years, 59% male, estimated glomerular filtration rate 51±18 mL/min/1.73 m2]. Time since transplantation was 5.8 (1.0-12.0) years. Prevalence of ID was 65%. ID was independently associated with lower scores for mental speed (std.β = -0.19, P = .02) and attention and executive functioning (std.β = -0.19, P = .02), and tended to be associated with worse memory (std.β = -0.16, P = .07). Lower plasma ferritin levels were associated with worse memory (std.β = 0.23, P = .007), mental speed (std.β = 0.34, P < .001), and attention and executive functioning (std.β = 0.30, P = .001). Lower TSAT was associated with worse memory (std.β = 0.19, P = .04) and mental speed (std.β = 0.27, P = .003), and tended to be associated with worse attention and executive functioning (std.β = 0.16, P = .08).ConclusionsIron-deficient KTRs performed worse on neurocognitive tasks measuring memory, mental speed, and attention and executive functioning. These findings set the stage for prospective studies addressing whether ID correction restores cognitive function after kidney transplantation.

Project description:BackgroundSurvival of kidney transplant recipients (KTR) is low compared with the general population. Low muscle mass and muscle strength may contribute to lower survival, but practical measures of muscle status suitable for routine care have not been evaluated for their association with long-term survival and their relation with each other in a large cohort of KTR.MethodsData of outpatient KTR ≥ 1 year post-transplantation, included in the TransplantLines Biobank and Cohort Study (ClinicalTrials.gov Identifier: NCT03272841), were used. Muscle mass was determined as appendicular skeletal muscle mass indexed for height2 (ASMI) through bio-electrical impedance analysis (BIA), and by 24-h urinary creatinine excretion rate indexed for height2 (CERI). Muscle strength was determined by hand grip strength indexed for height2 (HGSI). Secondary analyses were performed using parameters not indexed for height2. Cox proportional hazards models were used to investigate the associations between muscle mass and muscle strength and all-cause mortality, both in univariable and multivariable models with adjustment for potential confounders, including age, sex, body mass index (BMI), estimated glomerular filtration rate (eGFR) and proteinuria.ResultsWe included 741 KTR (62% male, age 55 ± 13 years, BMI 27.3 ± 4.6 kg/m2), of which 62 (8%) died during a median [interquartile range] follow-up of 3.0 [2.3-5.7] years. Compared with patients who survived, patients who died had similar ASMI (7.0 ± 1.0 vs. 7.0 ± 1.0 kg/m2; P = 0.57), lower CERI (4.2 ± 1.1 vs. 3.5 ± 0.9 mmol/24 h/m2; P < 0.001) and lower HGSI (12.6 ± 3.3 vs. 10.4 ± 2.8 kg/m2; P < 0.001). We observed no association between ASMI and all-cause mortality (HR 0.93 per SD increase; 95% confidence interval [CI] [0.72, 1.19]; P = 0.54), whereas CERI and HGSI were significantly associated with mortality, independent of potential confounders (HR 0.57 per SD increase; 95% CI [0.44, 0.81]; P = 0.002 and HR 0.47 per SD increase; 95% CI [0.33, 0.68]; P < 0.001, respectively), and associations of CERI and HGSI with mortality remained independent of each other (HR 0.68 per SD increase; 95% CI [0.47, 0.98]; P = 0.04 and HR 0.53 per SD increase; 95% CI [0.36, 0.76]; P = 0.001, respectively). Similar associations were found for unindexed parameters.ConclusionsHigher muscle mass assessed by creatinine excretion rate and higher muscle strength assessed by hand grip strength are complementary in their association with lower risk of all-cause mortality in KTR. Muscle mass assessed by BIA is not associated with mortality. Routine assessment using both 24-h urine samples and hand grip strength is recommended, to potentially target interdisciplinary interventions for KTR at risk for poor survival to improve muscle status.

Project description:BackgroundLong-term high-dose lithium therapy in bipolar disorder is known to adversely affect kidney function. However, recent animal studies have revealed that low amounts of lithium are beneficial for the kidney when it is damaged by exposure to nephrotoxic compounds, inflammation or oxidative stress. This study aimed to investigate whether urinary lithium excretion, reflecting dietary lithium intake, is associated with adverse long-term kidney graft outcomes and patient survival.MethodsUrinary lithium concentration was measured using inductively coupled plasma mass spectrometry in 642 stable kidney transplant recipients (KTRs). Graft failure was defined as the start of dialysis or retransplantation and kidney function decline was defined as a doubling of serum creatinine.ResultsThe median urinary lithium excretion was 3.03 μmol/24 h [interquartile range (IQR) 2.31-4.01]. Urinary lithium excretion was associated with energy, plant protein and water intake. During a median follow-up of 5.3 years (IQR 4.5-6.0), 79 (12%) KTRs developed graft failure and 127 (20%) KTRs developed kidney function decline. Higher urinary lithium excretion was associated with a lower risk of graft failure {hazard ratio [HR] per doubling 0.54 [95% confidence interval (CI) 0.38-0.79]} and kidney function decline [HR per doubling 0.73 (95% CI 0.54-0.99)]. These associations remained independent of adjustment for potential confounders and in sensitivity analyses. There was a significant effect modification with the use of proliferation inhibitors (P = .05) and baseline estimated glomerular filtration rate (eGFR; P < .001), with higher urinary lithium excretion being more protective in KTRs not using proliferation inhibitors and in KTRs with lower baseline eGFR. Furthermore, higher urinary lithium excretion was associated with a reduced risk of all-cause mortality [HR 0.64 (95% CI 0.49-0.83); P = .001].ConclusionDietary lithium intake may be a potentially modifiable, yet rather overlooked, risk factor for adverse long-term kidney graft outcomes and patient survival.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT02811835.

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Plasma Vitamin C and Risk of Late Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Biobank and Cohort Study.

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