Rationale and effect of reduction of immunosuppressive load in organ transplant recipients

Giving a patient immunosuppressive medication is creating an environment in which a transplanted organ will be accepted and rejection will be prevented. Unfortunately, the use of immunosuppression is complicated by serious side effects. After dealing with acute rejection in solid organ transplantation and reducing the incidence of infections in the early days of transplantation, other serious complications became more and more clear. The development of, for example, cardiovascular disease, diabetes mellitus, nephrotoxicity and malignancies after solid organ transplantation is a well known problem for every transplant clinician

Cardiac and metabolic effects in patients who present with a multinodular goitre

Twenty-six consecutive patients who presented with clinically euthyroid multinodular goitre were studied for an overnight fasting serum lipid profile and 24 h Holter monitoring. Mean serum TSH was 0.6 +/- 0.4 vs 2.4 +/- 1.3 mU/l (p < 0.0001) and mean TT3 2.4 +/- 0.4 vs 2.0 +/- 0.5 nmol/l (p = 0.009) in patients vs controls (n = 15) while mean FT4 was not different from controls. Total serum HDL, LDL cholesterol and triglycerides were lower in patients but creatinine, ferritin and SHBG levels did not differ between patients and controls. The 24-hour ambulatory continuous ECG recordings did not demonstrate significant differences in mean, minimal and maximal heart rate between the study and the control group. Nocturnal heart rate, measured between 23.00 and 06.00 hours, also showed no differences between the two groups. Atrial fibrillation was absent in both the study and the control group. Premature atrial and ventricular complexes occurred equally frequently in both groups. Comparison of patients with a serum TSH below 0.4 mU/l (n = 11) and patients with a TSH above 0.4 mU/l revealed no differences. In conclusion, in consecutive patients who present with multinodular goitre, effects were found on the lipid profile, but not on the heart. It is argued that in this type of patients, cardiac effects depend on the degree of subclinical hyperthyroidism

Attitudes among transplant professionals regarding shifting paradigms in eligibility criteria for live kidney donation

Background The transplant community increasingly accepts extended criteria live kidney donors, however, great (geographical) differences are present in policies regarding the acceptance of these donors, and guidelines do not offer clarity. The aim of this survey was to reveal these differences and to get an insight in both centre policies as well as personal beliefs of transplant professionals. Methods An online survey was sent to 1128 ESOT-members. Questions were included about several extended donor criteria; overweight/obesity, older age, vascular multiplicity, minors as donors and comorbidities; hypertension, impaired fasting glucose, kidney stones, malignancies and renal cysts. Comparisons were made between transplant centres of three regions in Europe and between Europe and other countries worldwide. Results 331 questionnaires were completed by professionals from 55 countries. Significant differences exist between regions in Europe in acceptance of donors with several extended criteria. Median refusal rate for potential live donors is 15%. Furthermore, differences are seen regarding pre-operative work-up, both in specialists who perform screening as in preoperative imaging. Conclusions Remarkably, 23.4% of transplant professionals sometimes deviate from their centre policy, resulting in more or less comparable personal beliefs regarding extended criteria. Variety is seen, proving the need for a standardized approach in selection, preferably evidence based

Effect of Pregnancy on eGFR after Kidney Transplantation:A National Cohort Study

BACKGROUND: The effect of pregnancy on the course of estimated glomerular filtration rate (eGFR) is unknown in kidney transplant recipients (KTRs). METHODS: We conducted a nationwide multicenter cohort study in KTRs with pregnancy (>20 weeks) after kidney transplantation (KT). Annual eGFR's after KT until death or graft loss and additional eGFR's before each pregnancy were collected according to protocol. Changes in eGFR slope before and after each pregnancy were analyzed by generalized estimating equations (GEE) multilevel analysis adjusted for transplant vintage. RESULTS: We included 3194 eGFR measurements before and after pregnancy in 109 (55%) KTRs with 1, 78 (40%) with 2 and 10 (5%) with 3 pregnancies after KT. Median follow-up after first delivery post-KT was 14 years (IQR 18 years). Adjusted mean eGFR pre-pregnancy was 59 ml/min/1.73m2 (SEM 1.72; 95% CI 56-63), after first pregnancy 56 ml/min/1.73m2 (SEM 1.70; 95% CI 53-60), after second pregnancy 56 ml/min/1.73m2 (SEM 2.19; 95% CI 51-60) and after third pregnancy 55 ml/min/1.73m2 (SEM 8.63; 95% CI 38-72). Overall eGFR slope after first, second and third pregnancy was not significantly worse than pre-pregnancy (p = 0.28). However, adjusted mean eGFR after first pregnancy was 2.8 ml/min/1.73m (p = 0.08) lower than pre-pregnancy. CONCLUSIONS: First pregnancy has a small, but no significant, effect on eGFR slope in KTR. Midterm hyperfiltration, a marker for renal reserve capacity, was associated with better eGFR and death-censored graft survival. In this KTR cohort with long-term follow-up, no significant effect of pregnancy on kidney function was detected

Telemedicine for Kidney Transplant Recipients:Current State, Advantages, and Barriers

Telemedicine is defined as the use of electronic information and communication technologies to provide and support healthcare at a distance. In kidney transplantation, telemedicine is limited but is expected to grow markedly in the coming y. Current experience shows that it is possible to provide transplant care at a distance, with benefits for patients like reduced travel time and costs, better adherence to medication and appointment visits, more self-sufficiency, and more reliable blood pressure values. However, multiple barriers in different areas need to be overcome for successful implementation, such as recipients' preferences, willingness, skills, and digital literacy. Moreover, in many countries, limited digital infrastructure, legislation, local policy, costs, and reimbursement issues could be barriers to the implementation of telemedicine. Finally, telemedicine changes the way transplant professionals provide care, and this transition needs time, training, willingness, and acceptance. This review discusses the current state and benefits of telemedicine in kidney transplantation, with the aforementioned barriers, and provides an overview of future directions on telemedicine in kidney transplantation.</p

Impact of Extraction Time during Donation after Circulatory Death Organ Procurement on Kidney Function after Transplantation in the Netherlands

Background:In The Netherlands, 60% of deceased-donor kidney offers are after donation after circulatory death. Cold and warm ischemia times are known risk factors for delayed graft function (DGF) and inferior allograft survival. Extraction time is a relatively new ischemia time. During procurement, cooling of the kidneys is suboptimal with ongoing ischemia. However, evidence is lacking on whether extraction time has an impact on DGF if all ischemic periods are included.Methods:Between 2012 and 2018, 1524 donation after circulatory death kidneys were procured and transplanted in The Netherlands. Donation and transplantation-related data were obtained from the database of the Dutch Transplant Foundation. The primary outcome parameter was the incidence of DGF. Results:In our cohort, extraction time ranged from 14 to 237 min, with a mean of 62 min (SD 32). In multivariate logistic regression analysis, extraction time was an independent risk factor for incidence of DGF (odds ratio per minute increase 1.008; 95% confidence interval, 1.003-1.013; P = 0.001). The agonal phase, hypoperfusion time, and anastomosis time were not independent risk factors for incidence of DGF. Conclusions:Considering all known ischemic periods during the donation after the circulatory death process, prolonged kidney extraction time increased the risk of DGF after kidney transplantation.</p

A nationwide Dutch cohort study shows relatively good pregnancy outcomes after kidney transplantation and finds risk factors for adverse outcomes

Although numbers of pregnancy after kidney transplantation (KT) are rising, high risks of adverse pregnancy outcomes (APO) remain. Though important for pre-conception counselling and pregnancy monitoring, analyses of pregnancy outcomes after KT per pre-pregnancy estimated glomerular filtration rate-chronic kidney disease (eGFR-CKD)-categories have not been performed on a large scale before. To do this, we conducted a Dutch nationwide cohort study of consecutive singleton pregnancies over 20 weeks of gestation after KT. Outcomes were analyzed per pre-pregnancy eGFR-CKD category and a composite APO (cAPO) was established including birth weight under 2500 gram, preterm birth under 37 weeks, third trimester severe hypertension (systolic blood pressure over 160 and/or diastolic blood pressure over 110 mm Hg) and/or over 15% increase in serum creatinine during pregnancy. Risk factors for cAPO were analyzed in a multilevel model after multiple imputation of missing predictor values. In total, 288 pregnancies in 192 women were included. Total live birth was 93%, mean gestational age 35.6 weeks and mean birth weight 2383 gram. Independent risk factors for cAPO were pre-pregnancy eGFR, midterm percentage serum creatinine dip and midterm mean arterial pressure dip; odds ratio 0.98 (95% confidence interval 0.96–0.99), 0.95 (0.93-0.98) and 0.94 (0.90-0.98), respectively. The cAPO was a risk indicator for graft loss (hazard ratio 2.55, 1.09-5.96) but no significant risk factor on its own when considering pre-pregnancy eGFR (2.18, 0.92-5.13). This was the largest and most comprehensive study of pregnancy outcomes after KT, including pregnancies in women with poor kidney function, to facilitate individualized pre-pregnancy counselling based on pre-pregnancy graft function. Overall obstetric outcomes are good. The risk of adverse outcomes is mainly dependent on pre-pregnancy graft function and hemodynamic adaptation to pregnancy

Modelling changes in the pharmacokinetics of tacrolimus during pregnancy after kidney transplantation:A retrospective cohort study

Aims: Pregnancy after kidney transplantation is realistic but immunosuppressants should be continued to prevent rejection. Tacrolimus is safe during pregnancy and is routinely dosed based on whole-blood predose concentrations. However, maintaining these concentrations is complicated as physiological changes during pregnancy affect tacrolimus pharmacokinetics. The aim of this study was to describe tacrolimus pharmacokinetics throughout pregnancy and explain the changes by investigating covariates in a population pharmacokinetic model. Methods: Data of pregnant women using a twice-daily tacrolimus formulation following kidney transplantation were retrospectively collected from 6 months before conception, throughout gestation and up to 6 months postpartum. Pharmacokinetic analysis was performed using nonlinear mixed effects modelling. Demographic, clinical and genetic parameters were evaluated as covariates. The final model was evaluated using goodness-of-fit plots, visual predictive checks and a bootstrap analysis. Results: A total of 260 whole-blood tacrolimus predose concentrations from 14 pregnant kidney transplant recipients were included. Clearance increased during pregnancy from 34.5 to 41.7 L/h, by 15, 19 and 21% in the first, second and third trimester, respectively, compared to prior to pregnancy. This indicates a required increase in the tacrolimus dose by the same percentage to maintain the prepregnancy concentration. Haematocrit and gestational age were negatively correlated with tacrolimus clearance (P ≤ 0.01), explaining 18% of interindividual and 85% of interoccasion variability in oral clearance.Conclusions: Tacrolimus clearance increases during pregnancy, resulting in decreased exposure to tacrolimus, which is explained by gestational age and haematocrit. To maintain prepregnancy target whole-blood tacrolimus predose concentrations during pregnancy, increasing the dose is required.</p

Long-Term Kidney and Maternal Outcomes After Pregnancy in Living Kidney Donors

For counseling it is important to know if pregnancy after Living Kidney Donation (LKD) affects long-term outcomes of the mono-kidney and the mother. Therefore, we performed a retrospective multicenter study in women ≤45 years who donated their kidney between 1981 and 2017. Data was collected via questionnaires and medical records. eGFR of women with post-LKD pregnancies were compared to women with pre-LKD pregnancies or nulliparous. eGFR before and after pregnancy were compared in women with post-LKD pregnancies. Pregnancy outcomes post-LKD were compared with pre-LKD pregnancy outcomes. 234 women (499 pregnancies) were included, of which 20 with pre- and post-LKD pregnancies (68) and 26 with only post-LKD pregnancies (59). Multilevel analysis demonstrated that eGFR was not different between women with and without post-LKD pregnancies (p = 0.23). Furthermore, eGFR was not different before and after post-LKD pregnancy (p = 0.13). More hypertensive disorders of pregnancy (HDP) occurred in post-LKD pregnancies (p = 0.002). Adverse fetal outcomes did not differ. We conclude that, despite a higher incidence of HDP, eGFR was not affected by post-LKD pregnancy. In line with previous studies, we found an increased risk for HDP after LKD without affecting fetal outcome. Therefore, a pregnancy wish alone should not be a reason to exclude women for LKD.</p