The TransplantLines Biobank and Cohort Study (NCT03272841) is an ongoing prospective study conducted at the University Medical Centre Groningen, The Netherlands. TransplantLines aims to identify risk factors and biomarkers associated with health problems following solid organ transplantation and donation. Additionally, the study seeks to develop new interventions to reduce symptom burden and improve long-term outcomes, including health-related quality of life, cardiovascular complications, graft failure, and mortality. It includes recipients of (combined) heart, liver, lung, kidney, pancreas, and small bowel transplants, as well as living liver and kidney donors, and deceased (multi-)organ donors. The biobank contains a wide range of biomaterials including whole blood, serum, EDTA-plasma, buffy coat, 24-h urine samples, faeces, hair, nails, and tissues. Data collection includes physical and cognitive assessments, extensive laboratory analysis, metagenomic sequencing, and questionnaires. TransplantLines, initiated in 2015, consists of 5143 participants as of October 2024, among 2312 (45%) females. The mean age was 50 (± 16) years at transplantation, 55 (± 11) years at living donation and 56 (± 15) years at deceased donation. Both cross-sectional and longitudinal biomaterials and data are included. For recipients, longitudinal biomaterials and data were collected at: pre-transplantation, at transplantation, and at 3, 6, 12, 24, and 60 months post-transplantation. For living donors, data were collected at pre-donation, donation, 3 months post-donation, and/or 5 or 10 years post-donation.

Torque Teno Virus (TTV) is a non-pathogenic virus that is highly prevalent among kidney transplant recipients (KTRs). Its circulating load is associated with an immunological status in KTR and is considered a promising tool for guiding immunosuppression. To allow for optimal guidance, it is important to identify other determinants of TTV load. We aimed to investigate the potential association of smoking and alcohol intake with TTV load. For this cross-sectional study, serum TTV load was measured using PCR in stable kidney transplant recipients at ≥1 year after transplantation, and smoking status and alcohol intake were assessed through questionnaires and measurements of urinary cotinine and ethyl glucuronide. A total of 666 KTRs were included (57% male). A total of 549 KTR (82%) had a detectable TTV load (3.1 ± 1.5 log₁₀ copies/mL). In KTR with a detectable TTV load, cyclosporin and tacrolimus use were positively associated with TTV load (St. β = 0.46, p < 0.001 and St. β = 0.66, p < 0.001, respectively), independently of adjustment for potential confounders. Current smoking and alcohol intake of >20 g/day were negatively associated with TTV load (St. β = −0.40, p = 0.004 and St. β = −0.33, p = 0.009, respectively), independently of each other and of adjustment for age, sex, kidney function, time since transplantation and calcineurin inhibitor use. This strong association of smoking and alcohol intake with TTV suggests a need to account for the smoking status and alcohol intake when applying TTV guided immunosuppression in KTR.

A potential contributor to fatigue in kidney transplant recipients (KTR) may be impaired creatine homeostasis. We developed and validated a high-throughput NMR assay allowing for simultaneous measurement of circulating creatine and creatinine, and determined plasma creatine and estimated intramuscular creatine concentrations in KTRs, delineated their determinants and explored their associations with self-reported fatigue. An NMR assay was developed and validated for measurement of circulating creatinine and creatine. Plasma creatine and creatinine concentrations were measured in 618 KTR. Fatigue was assessed using the checklist individual strength. Associations of creatine parameters with fatigue was assessed using linear mixed effect models. The NMR-based assay had good sensitivity, precision and demonstrated linearity across a large range of values. Among KTR, the mean age was 56±13 years, 62% were and eGFR was 54±18 ml/min/1.73m². Plasma creatine concentration was 27 [19-39] µmol/L. Estimated intramuscular creatine concentration was 27±7 mmol/kg. Higher plasma creatine concentration and higher estimated intramuscular creatine concentration were independently associated with a lower total fatigue score and less motivation problems. An NMR method for measurement of circulating creatine and creatinine which offers the potential for accurate and efficient quantification was developed. The found associations indicate that improving creatine status may play a beneficial role in mitigating fatigue.

Torque teno virus (TTV) is emerging as a potential marker for monitoring immune status. In transplant recipients who are immunosuppressed, higher TTV DNA loads are observed than in healthy individuals. TTV load measurement may aid in optimizing immunosuppressive medication dosing in solid organ transplant recipients. Additionally, there is a growing interest in the role of HDL particles in immune function; therefore, assessment of both HDL concentrations and TTV load may be of interest in transplant recipients. The objective of this study was to analyze TTV loads and HDL parameters in serum samples collected at least one year post-transplantation from 656 stable outpatient kidney transplant recipients (KTRs), enrolled in the TransplantLines Food and Nutrition Cohort (Groningen, the Netherlands). Plasma HDL particles and subfractions were measured using nuclear magnetic resonance spectroscopy. Serum TTV load was measured using a quantitative real-time polymerase chain reaction. Associations between HDL parameters and TTV load were examined using univariable and multivariable linear regression. The median age was 54.6 [IQR: 44.6 to 63.1] years, 43.3% were female, the mean eGFR was 52.5 (±20.6) mL/min/1.73 m² and the median allograft vintage was 5.4 [IQR: 2.0 to 12.0] years. A total of 539 participants (82.2%) had a detectable TTV load with a mean TTV load of 3.04 (±1.53) log10 copies/mL, the mean total HDL particle concentration was 19.7 (±3.4) μmol/L, and the mean HDL size was 9.1 (±0.5) nm. The univariable linear regression revealed a negative association between total HDL particle concentration and TTV load (st.β = −0.17, 95% CI st.β: −0.26 to −0.09, p < 0.001). An effect modification of smoking behavior influencing the association between HDL particle concentration and TTV load was observed (P_interaction = 0.024). After adjustment for age, sex, alcohol intake, hemoglobin, eGFR, donor age, allograft vintage and the use of calcineurin inhibitors, the negative association between HDL particle concentration and TTV load remained statistically significant in the non-smoking population (st.β = −0.14, 95% CI st.β: −0.23 to −0.04, p = 0.006). Furthermore, an association between small HDL particle concentration and TTV load was found (st.β = −0.12, 95% CI st.β: −0.22 to −0.02, p = 0.017). Higher HDL particle concentrations were associated with a lower TTV load in kidney transplant recipients, potentially indicative of a higher immune function. Interventional studies are needed to provide causal evidence on the effects of HDL on the immune system.

Patients with chronic kidney disease (CKD) are at risk for vitamin C (VitC) deficiency. We aimed to investigate VitC status and its determinants across the spectrum of CKD and healthy individuals. In this cross-sectional study, we measured plasma VitC concentrations (<10μmol/L=deficient, 10-35μmol/L=inadequate) in 62 individuals on dialysis, 41 with CKD stage 4/5, 42 kidney transplant recipients (KTR) (together: CKD population), and in 447 living kidney donors (KD), and 385 healthy controls (HC) (together: healthy population). In the CKD population we assessed VitC intake (<75 mg/day=inadequate) using 24-hour dietary recalls. We measured VitC removal by hemodialysis. We investigated potential determinants of plasma VitC with linear regression in the CKD population and in healthy population separately. Median [Q1-Q3] plasma VitC was highest in HC (58 [43-69] μmol/L, 14% inadequate/deficient), followed by KD (50 [36-66] μmol/L, 22% inadequate/deficient), KTR (37 [19-46] μmol/L, 48% inadequate/deficient), dialysis (33 [19-47] μmol/L, 58% inadequate/deficient), and CKD stage 4/5 (22 [14-34] μmol/L, 80% inadequate/deficient). Daily dietary VitC intake was similar in KTR (55.5 [33.5-144.2] mg, 55% inadequate) and CKD stage 4/5 (53.0 [23.9-142.0] mg, 56% inadequate), and higher in dialysis (113 [72-209] mg, 26% inadequate) due to supplementation. VitC removal was 58 [27-123] mg in conventional and 128 [97-156] mg in nocturnal hemodialysis sessions. In the healthy population, eGFR was positively associated with plasma VitC (st. β=0.18 (0.08, 0.27), p<0.001), independent of potential confounders. VitC inadequacy and deficiency are common in CKD. Inadequate intake and removal by dialysis may contribute. In healthy individuals eGFR was inversely associated with plasma VitC. Our findings highlight the importance of monitoring VitC status in CKD, and represent a potential target for intervention. Future research could evaluate potential health effects of improving VitC status in CKD.