Remnant lipoprotein cholesterol is associated with incident new onset diabetes after transplantation (NODAT) in renal transplant recipients:results of the TransplantLines Biobank and cohort Studies

BACKGROUND: New onset diabetes after transplantation (NODAT) is a frequent and serious complication of renal transplantation resulting in worse graft and patient outcomes. The pathophysiology of NODAT is incompletely understood, and no prospective biomarkers have been established to predict NODAT risk in renal transplant recipients (RTR). The present work aimed to determine whether remnant lipoprotein (RLP) cholesterol could serve as such a biomarker that would also provide a novel target for therapeutic intervention. METHODS: This longitudinal cohort study included 480 RTR free of diabetes at baseline. 53 patients (11%) were diagnosed with NODAT during a median [interquartile range, IQR] follow-up of 5.2 [4.1–5.8] years. RLP cholesterol was calculated by subtracting HDL and LDL cholesterol from total cholesterol values (all directly measured). RESULTS: Baseline remnant cholesterol values were significantly higher in RTR who subsequently developed NODAT (0.9 [0.5–1.2] mmol/L vs. 0.6 [0.4–0.9] mmol/L, p = 0.001). Kaplan-Meier analysis showed that higher RLP cholesterol values were associated with an increased risk of incident NODAT (log rank test, p < 0.001). Cox regression demonstrated a significant longitudinal association between baseline RLP cholesterol levels and NODAT (HR, 2.27 [1.64–3.14] per 1 SD increase, p < 0.001) that remained after adjusting for plasma glucose and HbA1c (p = 0.002), HDL and LDL cholesterol (p = 0.008) and use of immunosuppressive medication (p < 0.001), among others. Adding baseline remnant cholesterol to the Framingham Diabetes Risk Score significantly improved NODAT prediction (change in C-statistic, p = 0.01). CONCLUSIONS: This study demonstrates that baseline RLP cholesterol levels strongly associate with incident NODAT independent of several other recognized risk factors

Mediterranean Style Diet and Kidney Function Loss in Kidney Transplant Recipients

Background and objectives Despite improvement of short-term graft survival over recent years, long-term graft survival after kidney transplantation has not improved. Studies in the general population suggest the Mediterranean diet benefits kidney function preservation. We investigated whether adherence to the Mediterranean diet is associated with kidney outcomes in kidney transplant recipients. Design, setting, participants, & measurements We included 632 adult kidney transplant recipients with a functioning graft for ≥1 year. Dietary intake was inquired using a 177-item validated food frequency questionnaire. Adherence to the Mediterranean diet was assessed using a nine-point Mediterranean Diet Score. Primary end point of the study was graft failure and secondary end points included kidney function decline (doubling of serum creatinine or graft failure) and graft loss (graft failure or death with a functioning graft). Cox regression analyses were used to prospectively study the associations of the Mediterranean Diet Score with study end points. Results During median follow-up of 5.4 (interquartile range, 4.9–6.0) years, 76 participants developed graft failure, 119 developed kidney function decline, and 181 developed graft loss. The Mediterranean Diet Score was inversely associated with all study end points (graft failure: hazard ratio [HR], 0.68; 95% confidence interval [95% CI], 0.50 to 0.91; kidney function decline: HR, 0.68; 95% CI, 0.55 to 0.85; and graft loss: HR, 0.74; 95% CI, 0.63 to 0.88 per two-point increase in Mediterranean Diet Score) independent of potential confounders. We identified 24-hour urinary protein excretion and time since transplantation to be an effect modifier, with stronger inverse associations between the Mediterranean Diet Score and kidney outcomes observed in participants with higher urinary protein excretion and participants transplanted more recently. Conclusions Adherence to the Mediterranean diet is associated with better kidney function outcomes in kidney transplant recipients.</p

High-density lipoprotein particles and their relationship to posttransplantation diabetes mellitus in renal transplant recipients

High concentrations of high-density lipoprotein (HDL) cholesterol are likely associated with a lower risk of posttransplantation diabetes mellitus (PTDM). However, HDL particles vary in size and density with yet unestablished associations with PTDM risk. The aim of our study was to determine the association between different HDL particles and development of PTDM in renal transplant recipients (RTRs). We included 351 stable outpatient adult RTRs without diabetes at baseline evaluation. HDL particle characteristics and size were measured by nuclear magnetic resonance (NMR) spectroscopy. During 5.2 (IQR, 4.1‒5.8) years of follow-up, 39 (11%) RTRs developed PTDM. In multivariable Cox regression analysis, levels of HDL cholesterol (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.40–0.94 per 1SD increase; p = 0.024) and of large HDL particles (HR 0.68, 95% CI 0.50–0.93 per log 1SD increase; p = 0.017), as well as larger HDL size (HR 0.58, 95% CI 0.36–0.93 per 1SD increase; p = 0.025) were inversely associated with PTDM development, independently of relevant covariates including, age, sex, body mass index, medication use, transplantation-specific parameters, blood pressure, triglycerides, and glucose. In conclusion, higher concentrations of HDL cholesterol and of large HDL particles and greater HDL size were associated with a lower risk of PTDM development in RTRs, independently of established risk factors for PTDM development

Low circulating concentrations of very long chain saturated fatty acids are associated with high risk of mortality in kidney transplant recipients

Kidney transplant recipients (KTR) are at increased risk of mortality, particularly from infectious diseases, due to lifelong immunosuppression. Although very long chain saturated fatty acids (VLSFA) have been identified as crucial for phagocytosis and clearance of infections, their association with mortality in immunocompromised patient groups has not been studied. In this prospective cohort study we included 680 outpatient KTR with a functional graft ≥1 year and 193 healthy controls. Plasma VLSFA (arachidonic acid (C20:0), behenic acid (C22:0) and lignoceric acid (C24:0)) were measured by gas chromatography coupled with a flame ionization detector. Cox regression analyses was used to prospectively study the associations of VLSFA with all-cause and cause-specific mortality. All studied VLSFA were significantly lower in KTR compared to healthy controls (all p < 0.001). During a median (interquartile range) follow-up of 5.6 (5.2–6.3) years, 146 (21%) KTR died, of which 41 (28%) died due to infectious diseases. In KTR, C22:0 was inversely associated with risk of all-cause mortality, with a HR (95% CI) per 1-SD-increment of 0.79 (0.64–0.99), independent of adjustment for potential confounders. All studied VLSFA were particularly strongly associated with mortality from infectious causes, with respective HRs for C20:0, C22:0 and C24:0 of 0.53 (0.35–0.82), 0.48 (0.30–0.75), and 0.51 (0.33–0.80), independent of potential confounders. VLSFA are inversely associated with infectious disease mortality in KTR after adjustment, including HDL-cholesterol. Further studies are needed to assess the effect of VLSFA-containing foods on the risk of infectious diseases in immunocompromised patient groups

Mediterranean style diet is associated with low risk of new-onset diabetes after renal transplantation

Objective: The incidence of new-onset diabetes after transplantation (NODAT) and premature mortality is high in renal transplant recipients (RTR). We hypothesized that a Mediterranean Style diet protects against NODAT and premature mortality in RTR. Research design and methods: A prospective cohort study of adult RTR with a functioning graft for >1 year. Dietary intake was assessed with a 177- item validated food frequency questionnaire. Patients were divided based on a 9-point Mediterranean Style Diet Score (MDS): low MDS (0-4 points) versus high MDS (5-9 points). A total of 468 RTR were eligible for analyses. Logistic multivariable regression analyses were used to study the association of MDS with NODAT and Cox multivariable regression models for the association with all-cause mortality. Results: Mean±SD age was 51.3±13.2 years and 56.6% were men. About 50% of the patients had a high MDS. During median follow-up of 4.0 (IQR, 0.4-5.4) years, 22 (5%) RTR developed NODAT and 50 (11%) died. High MDS was significantly associated with both a lower risk of NODAT (HR=0.23; 95% CI 0.09 to 0.64; p=0.004) and allcause mortality (HR=0.51; 95% CI 0.29 to 0.89, p=0.02) compared to low MDS, independent of age and sex. Adjustment for other potential confounders, including total energy intake, physical activity and smoking status, did not materially change the results of the analyses. Conclusions: Dietary habits leading to high MDS were associated with lower risk of NODAT. These results suggest that healthy dietary habits are of paramount importance for RTR

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