Long-term Kidney Transplant Recipients Research Articles

#1692 Prevalence and risk factors for persistent hyperparathyroidism in long-term kidney transplant recipients

Abstract Background and Aims Secondary hyperparathyroidism, associated with fractures and cardiovascular mortality in end-stage kidney disease, often resolves after kidney transplantation (KT). However, limited knowledge exists regarding persistent hyperparathyroidism (persist-PTH) after long-term KT. We aimed to define the prevalence and risk factors of persist-PTH in KT recipients at ≥3 years post-KT. Method A historical cohort study was conducted in adult KT recipients at Srinagarind Hospital, Khon Kaen University, Thailand, from 2015 to 2020. Persist-PTH is defined as serum parathyroid hormone (PTH) exceeding twice the upper limit of normal (>130 pg/mL) after ≥3 years post-KT. Results A total of 281 patients were included, with a median age of 41.4 years (interquartile range (IQR), 32.7-49.1), and 117 patients (41.6%) were female. The median post-KT follow-up was 71 months (IQR, 54-89) with a glomerular filtration rate (GFR) of 61.8 mL/min/1.73 m² (IQR, 48.2-76.9). The respective median pre-KT and post-KT PTH were 403 pg/mL (IQR, 196.3-862) and 96.7 pg/mL (IQR, 67.3-166). Post-KT PTH levels correlated with pre-KT PTH levels (r²=0.18; P<0.001). Persist-PTH occurred in 100 patients, with a prevalence of 35.6% (95% confidence interval (CI), 30.2-41.4%). Multivariate analysis revealed significant associations between persist-PTH and a longer dialysis vintage (odds ratio (OR) 1.13 per 6-month increase; 95% CI, 1.06-1.20; P<0.001), lower GFR (OR, 0.76 per 10 mL/min/1.73 m² increase; 95% CI, 0.63-0.92; P=0.004), and higher pre-KT PTH (HR, 1.06 per 50 pg/mL increase; 95% CI, 1.02-1.10; P=0.001). Furthermore, persist-PTH with hypercalcemia (>10.2 mg/dL) occurred in 44 patients (15.7%; 95% CI, 11.8-20.4%), and with hypophosphatemia (<2.5 mg/dL) in 23 patients (8.2%; 95% CI, 5.5-12.0%). Conclusion Persist-PTH occurred in over one-third of long-term post-KT recipients, particularly in those with extended dialysis vintage, impaired graft function, and elevated pre-KT PTH levels. This underscores the need for optimal pre-KT PTH control and vigilant graft function monitoring to prevent persist-PTH.

The Impact of ABCC2 -24C>T Gene Polymorphism on Graft Survival in Kidney Transplant Recipients.

Personalized medicine in kidney transplantation has the potential to improve outcomes and reduce complications. The aim of this study was to investigate the influence of single nucleotide polymorphisms in genes encoding metabolizing enzymes (CYP3A5) and transporters (ABCC2) on clinical outcomes (acute graft failure and/or acute tubular necrosis (ATN)) in kidney transplant recipients (KTR). This was a multicenter, retrospective cohort study where adult KTR who had undergone kidney transplantation between 2020 and 2021 and received tacrolimus-mycophenolate treatment were enrolled in the study. DNA was extracted from collected blood samples using a commercially available kit. CYP3A5*3, ABCC2 -24C>T and ABCC2 3972C>T SNP were determined by polymerase chain reaction. Of the total 39 patients included, nine (23.1%) KTR had an incidence of acute graft failure and/or ATN. A multiple logistic regression showed wildtype ABCC2 -24C>T C allele had a higher risk of developing acute graft rejection and/or ATN compared to the variant allele carriers (adjusted Odd Ratios [aOR]: 27.675, p = 0.038). Recipients who had delayed graft function (aOR: 49.214, p = 0.012) and a history of CMV infection (aOR: 18.097, p = 0.009) were at 49.2 and 18.1-times increased risk for acute graft failure and/or ATN, respectively. The large aOR was inevitable due to the small sample size and required cautious interpretation. This is the first study to determine the effect of the ABCC2 -24C>T genetic polymorphism on clinical outcomes in Malaysian KTR and forms the basis for further work on ABCC2 -24C>T effects in long-term KTR.

Prevalence and risk factors of frailty in long-term kidney transplant recipients: a prospective study

Prevalence and risk factors of frailty in long-term kidney transplant recipients: a prospective study

Bone Disease in Kidney Transplantation: How Are the Bones of Long-Term Kidney Transplant Recipients?

Bone Disease in Kidney Transplantation: How Are the Bones of Long-Term Kidney Transplant Recipients?

Coexistence of Low Muscle Mass and Osteoporosis as a Predictor of Fragility Fractures in Long-Term Kidney Transplant Recipients

Introduction: Sarcopenia and osteoporosis are highly prevalent among kidney transplant recipients (KTRs). Although osteoporosis is known to increase fracture risk in KTRs, it is unclear whether sarcopenia or osteosarcopenia is associated with this increased risk. Thus, we aimed to investigate the association of the coexistence of low muscle mass (LMM) and osteoporosis with the risk of fracture in long-term KTRs. Methods: Exactly 342 stable KTRs underwent dual-energy X-ray absorptiometry and skeletal muscle mass index (SMI) measurement using bioelectrical impedance analysis. Results: LMM and osteoporosis were observed in 109 (31.9%) and 93 patients (27.2%), respectively. During a follow-up period of 5.1 years, 48 (14.0%) fractures occurred. KTRs with LMM had a higher fracture risk, but this was not significant (adjusted hazard ratio [aHR] 1.82, 95% confidence interval [CI] 0.94–3.50, p = 0.073). Similar results were obtained in KTRs with osteoporosis (aHR 1.84, 95% CI 0.96–3.47, p = 0.063). We divided the KTRs into four groups according to the presence of LMM and/or osteoporosis. The cumulative incidence rates of fractures were 13.0%, 11.1%, 10.5%, and 31.3% in the KTRs without both LMM and osteoporosis, those with LMM alone, those with osteoporosis alone, and those with both, respectively. The KTRs with both LMM and osteoporosis had a 2.92fold higher risk of fractures (95% CI 1.29–6.49; p = 0.010) than those without both LMM and osteoporosis. Conclusion: Long-term KTRs with the coexistence of LMM and osteoporosis had an independently higher risk of fragility fractures than those without both LMM and osteoporosis. The combination of SMI and osteoporosis definitions can be used to identify KTRs with a high fracture risk.

The Impact of Cholecaciferol Supplementation on Bone Mineral Density in Long-Term Kidney Transplant Recipients

Although reduced bone mineral density (BMD) is associated with a higher risk of fractures, morbidity, and mortality in kidney transplant patients (KTRs), there is no consensus on optimal treatment for the alterations of BMD in this population. This study aims at assessing the effect of cholecalciferol supplementation on BMD over a follow-up period of 2 years in a cohort of long-term KTRs. Patients with age ≥ 18 years were included and divided into two subgroups based on treatment with bisphosphonate and/or calcimimetics and/or active vitamin D sterols (KTRs-treated) or never treated with the above medications (KTRs-free). BMD was evaluated at lumbar vertebral bodies (LV) and right femoral neck (FN) with standard DEXA at the beginning and end of the study. According to World Health Organization (WHO) criteria, results were expressed as T-score and Z-score. Osteoporosis and osteopenia were defined as T score ≤ -2.5 SD and T score < -1 and >-2.5 SD, respectively. Cholecalciferol was supplemented at a dose of 25,000 IU/week over 12 weeks followed by 1500 IU/day. KTRs-free (n. 69) and KTRs-treated (n. 49) consecutive outpatients entered the study. KTRs-free were younger (p < 0.05), with a lower prevalence of diabetes (p < 0.05) and of osteopenia at FN (46.3 % vs. 61.2 %) compared to KTRs-treated. At the entry none of the study subjects had a sufficient level of cholecalciferol; Z-score and T-score at LV and FN were not different between groups. At the end of the study period, serum cholecalciferol concentration was significantly increased in both groups (p < 0.001); the KTRs-free group presented an improvement in both T-score and Z-score at LV (p < 0.05) as well as a lower prevalence of osteoporotic cases (21.7% vs. 15.9%); in contrast, no changes were recorded in KTR-treated individuals. In conclusion, supplementation with cholecalciferol ameliorated Z-score and T-score at LV in long-term KTRs who had been never treated with active or inactive vitamin D sterols, bisphosphonates, and calcimimetics. Future endeavours are needed to confirm these preliminary findings.

Sodium bicarbonate for kidney transplant recipients with metabolic acidosis in Switzerland: a multicentre, randomised, single-blind, placebo-controlled, phase 3 trial

Metabolic acidosis is common in kidney transplant recipients and is associated with declining graft function. Sodium bicarbonate treatment effectively corrects metabolic acidosis, but no prospective studies have examined its effect on graft function. Therefore, we aimed to test whether sodium bicarbonate treatment would preserve graft function and slow the progression of estimated glomerular filtration rate (GFR) decline in kidney transplant recipients. The Preserve-Transplant Study was a multicentre, randomised, single-blind, placebo-controlled, phase 3 trial at three University Hospitals in Switzerland (Zurich, Bern, and Geneva), which recruited adult (aged ≥18 years) male and female long-term kidney transplant recipients if they had undergone transplantation more than 1 year ago. Key inclusion criteria were an estimated GFR between 15 mL/min per 1·73 m2 and 89 mL/min per 1·73 m2, stable allograft function in the last 6 months before study inclusion (<15% change in serum creatinine), and a serum bicarbonate of 22 mmol/L or less. We randomly assigned patients (1:1) to either oral sodium bicarbonate 1·5-4·5 g per day or matching placebo using web-based data management software. Randomisation was stratified by study centre and gender using a permuted block design to guarantee balanced allocation. We did multi-block randomisation with variable block sizes of two and four. Treatment duration was 2 years. Acid-resistant soft gelatine capsules of 500 mg sodium bicarbonate or matching 500 mg placebo capsules were given at an initial dose of 500 mg (if bodyweight was <70 kg) or 1000 mg (if bodyweight was ≥70 kg) three times daily. The primary endpoint was the estimated GFR slope over the 24-month treatment phase. The primary efficacy analyses were applied to a modified intention-to-treat population that comprised all randomly assigned participants who had a baseline visit. The safety population comprised all participants who received at least one dose of study drug. The trial is registered with ClinicalTrials.gov, NCT03102996. Between June 12, 2017, and July 10, 2019, 1114 kidney transplant recipients with metabolic acidosis were assessed for trial eligibility. 872 patients were excluded and 242 were randomly assigned to the study groups (122 [50%] to the placebo group and 120 [50%] to the sodium bicarbonate group). After secondary exclusion of two patients, 240 patients were included in the intention-to-treat analysis. The calculated yearly estimated GFR slopes over the 2-year treatment period were a median -0·722 mL/min per 1·73 m2 (IQR -4·081 to 1·440) and mean -1·862 mL/min per 1·73 m2 (SD 6·344) per year in the placebo group versus median -1·413 mL/min per 1·73 m2 (IQR -4·503 to 1·139) and mean -1·830 mL/min per 1·73 m2 (SD 6·233) per year in the sodium bicarbonate group (Wilcoxon rank sum test p=0·51; Welch t-test p=0·97). The mean difference was 0·032 mL/min per 1·73 m2 per year (95% CI -1·644 to 1·707). There were no significant differences in estimated GFR slopes in a subgroup analysis and a sensitivity analysis confirmed the primary analysis. Although the estimated GFR slope did not show a significant difference between the treatment groups, treatment with sodium bicarbonate effectively corrected metabolic acidosis by increasing serum bicarbonate from 21·3 mmol/L (SD 2·6) to 23·0 mmol/L (2·7) and blood pH from 7·37 (SD 0·06) to 7·39 (0·04) over the 2-year treatment period. Adverse events and serious adverse events were similar in both groups. Three study participants died. In the placebo group, one (1%) patient died from acute respiratory distress syndrome due to SARS-CoV-2 and one (1%) from cardiac arrest after severe dehydration following diarrhoea with hypotension, acute kidney injury, and metabolic acidosis. In the sodium bicarbonate group, one (1%) patient had sudden cardiac death. In adult kidney transplant recipients, correction of metabolic acidosis by treatment with sodium bicarbonate over 2 years did not affect the decline in estimated GFR. Thus, treatment with sodium bicarbonate should not be generally recommended to preserve estimated GFR (a surrogate marker for graft function) in kidney transplant recipients with chronic kidney disease who have metabolic acidosis. Swiss National Science Foundation.

The CD226/TIGIT axis is involved in T cell hypo-responsiveness appearance in long-term kidney transplant recipients

T cell exhaustion refers to a dysfunctional state in which effector T cells present a decreased ability to proliferate and to produce cytokines, while the co-expression of inhibitory receptors increases. We investigated global and donor-specific T cell responses in a cohort of stable, living-donor kidney transplant patients that received similar immunosuppression. After transplantation, an increase in the ratio of TIGIT + /CD226 + in mCD4 + T cells (r = 0.47, p = 0.01), and a decrease of CD226 + TIGIT-mCD4 + T cells was observed (r = − 0.55, p = 0.001). This leads to an increase of dysfunctional T cells in patients far from transplantation. In mCD8 + T cells, a decrease of IL-2 production after mitogenic stimulation was observed far from transplantation. Phenotypic analyses revealed an increase of mCD8 + T cells co-expressing PD-1 and TIGIT over time (r = 0.51, p = 0.02). After donor-specific stimulation, the ability of CD4 + T cells to proliferate was decreased compared with third parties. CD4 + T cells expressing CD226 and TIGIT were correlated with allospecific CD4 + proliferation (r = 0.68, p = 0.04). Our study suggests that after kidney transplantation a T cell hyporesponsiveness appears over time, driven by a dysregulation of CD226/TIGIT axis in mCD4 + T cells, associated with an increase of PD1 + TIGIT + in mCD8 + T cells.

Relationship between Access to Nutrition and Visceral Adiposity in Stable Long-Term Inner City Kidney Transplant Recipients (KTRs)

ObjectivesHigher % body fat has been associated with increased risk for multiple diseases especially if it has a visceral distribution. We studied body fat patterns in a population of inner-city KTRs at risk for food scarcity to explore access to nutrition and its relationship to % body fat.MethodsA random sample of 16 stable long-term pts from kidney transplant clinic were studied using the InBody S10 body composition analyzer at a regularly scheduled appointment. Pts were seated and electrodes were attached to the middle fingers, thumbs and below each ankle. Food scarcity was assessed by a standardized survey.Results63% (10) pts had body fat >25% (HIFAT). They did not differ from pts with body fat <25% (6 pts, LOFAT) in time since transplant (mean 10.6 ± 4.0 yrs), race, education, or annual income. 12 (75%) pts identified as black, 2 (12.5%) white and 2 (12.5%) other. The majority (56.3%) had an annual income < $20 k. HIFAT pts had higher visceral fat (14.0 ± 1.3 vs 5.1 ± 1.3, p < 0.001), higher BMI (34.8 ± 1.25 vs 27.7 ± 1.7, p = 0.002), and body weight (227.1 ± 12.6 vs 180.5 ± 12.1, p = 0.01), but no difference in skeletal muscle mass. HIFAT pts were more likely to be male (70% vs 30%, p = 0.039) and were older (53.9 ± 2.7 vs 43.5 ± 2.5 yrs, p = 0.01). Pts with diabetes were more likely to be HIFAT than those without (100% vs 50%, p = 0.037). 50% of pts in the LOFAT group reported they had cut down or skipped meals because there wasn't enough money for food vs none of the HIFAT pts (p = 0.018). Additionally, 100% of pts who received food from a bank, church or pantry in the last year were LOFAT (p = 0.004). There was no difference in SNAP use between the two groups.ConclusionsIn our population of long-term inner-city KTRs a majority of patients had high total body fat, meeting the definition of obesity by BMI and pts with higher body fat weighed more overall with more visceral fat but not higher skeletal muscle mass. Patients with lower body fat reported more food scarcity and reliance on food pantries. Lower body fat in this population may not be related to better dietary habits and education regarding nutritional lifestyle changes that might improve body composition is important in this population at high risk for cardiovascular disease and diabetes.Funding SourcesUnfunded.

MO1011: The Effect of Vitamin D on Bone Mineral Density: A Real-Life Study in Long-Term Kidney Transplant Recipients Never Supplemented

Abstract BACKGROUND AND AIMS Vitamin D insufficiency has been associated with decreased bone mineral density (BMD) in kidney transplant patients (KTRs). However, few data on BMD changes due to vitamin D supplementation in long-term KTRs are available. The purpose of our study is to ascertain the effect of 25-OH-vitamin D (25-OH-D) supplementation on the BMD over a follow-up period of up to 3 years in a real-life cohort of long-term KTRs never supplemented with 25-OH-D and not treated with active vitamin D, bisphosphonate and calciomimetics. METHOD Demographic, clinical and laboratory data were collected. Inclusion criteria were: (1) being a recipient of a kidney from a cadaveric or living donor, (2) age ≥ 18 years and (3) no therapy with inactive vitamin D sterols. Patients with parathyroidectomy and/or history of bone fractures were excluded. BMD was evaluated with standard DEXA, performed at baseline (before vitamin D supplementation) and at the end of the study period. BMD was assessed at lumbar vertebral bodies (LV) and right femoral neck (FN) by a single operator. Bone mineral content (BMC) was calculated in grams (g), bone area in centimetres squared (cm2), and BMD in g/cm2 (BMC divided by the area). According to WHO criteria, results were expressed as T-score [standard deviation (SD) relative to young healthy adults] and Z-score (SD relative to age-matched controls). Osteoporosis and osteopenia were defined as T-score ≤−2.5 SD and T-score &amp;lt;−1 and &amp;gt;−2.5 SD, respectively. According to plasma levels, 25-OH-D was supplemented as recommended for the general population. Linear mixed model analysis was implemented to test the impact of 25-OH-D use on Z-score, T-score and BMD changes (dependent variables) adjusted for sex, age, BMI and presence of diabetes. Z-score, T-score and BMD changes were defined as Z-score, T-score and BMD at follow-up, Z-score, T-score and BMD at study inception. RESULTS A total of 118 KTRs consecutive outpatients never supplemented with 25-OH-D, of whom 69 KTRs were untreated (KTRs-free) and 49 were treated (control group) with bisphosphonate (n = 13) and/or calcio-mimetics (n = 11) and/or active vitamin D (n = 29) were enrolled. Clinical and biochemical characteristics are shown in Table 1. At the basal DEXA, the percentage of osteopenia and osteoporosis was 39.0% and 21.2% at LV; 52.5% and 16.9% at FN, respectively. The mean study-period was 27.7 ± 3.4 months. Basal and follow-up Z-score, T-score and BMD at both measurement sites are reported in Table 2. In linear mixed model analysis, a positive interaction of 25-OH-D supplementation on T-score and Z-score changes at the lumbar vertebral bodies was found (P &amp;lt; .05). At the end of the study, no statistical differences in Z-score, T-score and BMD gains were observed. CONCLUSION Prolonged supplementation with 25-OH-D affects Z-score and T-score at LV in long-term KTRs never supplemented with active or inactive vitamin D.

192 Visceral Adiposity and Relationship to Food Insecurity in Stable Long-term Inner City Kidney Transplant Recipients (KTRs)

192 Visceral Adiposity and Relationship to Food Insecurity in Stable Long-term Inner City Kidney Transplant Recipients (KTRs)

Collateral Effects and Mortality of Kidney Transplant Recipients during the COVID-19 Pandemic.

Collateral effects and consequences of the coronavirus disease 19 (COVID-19) pandemic on kidney transplant recipients remain widely unknown. This retrospective cohort study examined changes in admission rates, incidences of diseases leading to hospitalization, in-patient procedures, and maintenance medication in long-term kidney transplant recipients with functioning graft during the early COVID-19 pandemic in Germany. Data were derived from a nationwide health insurance database. Analysis was performed from March 15 to September 30 and compared the years 2019 and 2020. Effects on mortality and adverse allograft events were compared with COVID-19-attributed effects. A total of 7725 patients were included in the final analysis. Admissions declined in 2020 by 17%, with the main dip during a 3-month lockdown (-31%) but without a subsequent rebound. Incidences for hospitalization did not increase for any investigated disease entities, whereas decreasing trends were noted for non-COVID-19 pulmonary and urogenital infections (incidence rate ratio 0.8, 95% CI, 0.62 to 1.03, and 0.82, 95% CI, 0.65 to 1.04, respectively). Non-COVID-19 hospital stays were 0.6 days shorter (P=0.03) and not complicated by increased dialysis, ventilation, or intensive care treatment rates. In-hospital and 90-day mortality remained stable. Incidences of severe COVID-19 requiring hospitalization was 0.09 per 1000 patient-days, and in-hospital mortality was 9%. A third (31%) of patients with calcineurin-inhibitor medication and without being hospitalized for COVID-19 reduced doses by at least 25%, which was associated with an increased allograft rejection risk (adjusted hazard ratio 1.29, 95% CI, 1.02 to 1.63). COVID-19 caused 17% of all deaths but had no significant association with allograft rejections. All-cause mortality remained stable (incidence rate ratio 1.15, 95% CI, 0.91 to 1.46), also when restricting analysis to patients with no or outpatient-treated COVID-19 (0.97, 95% CI, 0.76 to 1.25). Despite significant collateral effects, mortality remained unchanged during the early COVID-19 pandemic. Considerable temporary reductions in admissions are safe, whereas reducing immunosuppression results in increased allograft rejection risk.

Bone Mineral Density Changes in Long-Term Kidney Transplant Recipients: A Real-Life Cohort Study of Native Vitamin D Supplementation.

Vitamin D insufficiency has been associated with reduced bone mineral density (BMD) in kidney transplant patients (KTRs). However, the efficacy of vitamin D supplementation on BMD remains poorly defined, especially for long-term KTRs. We aimed to investigate the effect of native vitamin D supplementation on the BMD of KTRs during a 2-year follow-up. Demographic, clinical, and laboratory data were collected. BMD was evaluated with standard DEXA that was performed at baseline (before vitamin D supplementation) and at the end of study period. BMD was assessed at lumbar vertebral bodies (LV) and right femoral neck (FN) by a single operator. According to WHO criteria, results were expressed as the T-score (standard deviation (SD) relative to young healthy adults) and Z-score (SD relative to age-matched controls). Osteoporosis and osteopenia were defined as a T-score ≤ −2.5 SD and a T-score < −1 and a > −2.5 SD, respectively. Based on plasma levels, 25-OH-vitamin D (25-OH-D) was supplemented as recommended for the general population. Data from 100 KTRs were analyzed. The mean study period was 27.7 ± 3.4 months. At study inception, 25-OH-D insufficiency and deficiency were recorded in 65 and 35 patients. At the basal DEXA, the percentage of osteopenia and osteoporosis was 43.3% and 18.6% at LV and 54.1% and 12.2% at FN, respectively. At the end of the study, no differences in the Z-score and T-score gains were observed. During linear mixed model analysis, native vitamin D supplementation was found to have a negative nitration with Z-score changes at the right femoral neck in KTRs (p < 0.05). The mean dose of administered cholecalciferol was 13.396 ± 7.537 UI per week; increased 25-OH-D levels were found (p < 0.0001). Either low BMD or 25-OH-vitamin D concentration was observed in long-term KTRs. Prolonged supplementation with 25-OH-D did not modify BMD, Z-score, or T-score.

Soluble Complement Component 1q Receptor 1 (sCD93) Is Associated with Graft Function in Kidney Transplant Recipients.

Cluster of differentiation 93 (CD93), also known as complement component 1q receptor 1 is a transmembrane glycoprotein expressed in endothelial and hematopoietic cells and associated with phagocytosis, cell adhesion, angiogenesis and inflammation. The extracellular part, soluble CD93 (sCD93), is released to body fluids in inflammation. Data on sCD93 in kidney diseases are limited. Our aim was to evaluate serum sCD93 in long-term kidney transplant recipients as a marker of inflammation and endothelial dysfunction that may be potentially useful in early recognition of graft dysfunction. Seventy-eight adult patients with functioning kidney graft and stable clinical state were examined at least one year after kidney transplantation. Serum sCD93 was measured by enzyme immunosorbent assay. Estimated glomerular filtration rate (eGFR) and albuminuria or proteinuria were assessed at baseline and over one-year follow-up. Increased sCD93 was associated with lower baseline eGFR independently of the confounders. Moreover, sCD93 was negatively associated with eGFR during one-year follow-up in simple analysis; however, this was not confirmed after adjustment for confounders. Baseline sCD93 was positively associated with baseline albuminuria and with increased proteinuria during the follow-up. Serum sCD93 was not correlated with other studied inflammatory markers (interleukin 6, C-reactive protein, procalcitonin and C3 and C4 complement components). To the best of our knowledge, this is the first report regarding the concentrations of sCD93 in kidney transplant recipients and one of the first reports showing the inverse association between sCD93 and renal function. Serum sCD93 should be further evaluated as a diagnostic and prognostic marker in renal transplantation.

Case Report: Severe COVID-19 in a Kidney Transplant Recipient Without Humoral Response to SARS-CoV-2 mRNA Vaccine Series.

Supplemental Digital Content is available in the text.

POS-701 OVER TEN-YEARS KIDNEY GRAFT SURVIVAL DETERMINANTS : A SINGLE CENTER EXPERIENCE

Renal transplantation is the treatment of choice for patients with end-stage kidney disease, offering cost, quality of life, and survival benefits over the alternative of dialysis. Over the past few decades surgical and medical advances have led to continuous improvement in short term graft survival, but this progress has not been accompanied by similar improvements in long-term graft survival and kidney transplant recipients continue to experience late allograft failure. The aim of this study was to estimate long-term survival rate of kidney transplantation and to detect associated prognostic factors. This is a retrospective study included adults who underwent kidney transplantation between 1995 and 2008 in the nephrology department of the Fattouma Bourguiba Hospital in Monastir (Tunisia). They were followed until 31 December 2018.Therefore, this cohort was followed for at least 10 years. Data were collected from patients’ medical records using a checklist. We compared the demographic, clinical, immunological, and laboratory profile of patients who had functional grafts ≥ 10 years after kidney transplantation to those whose transplants survived <10 years. Kaplan-Meier curve, log-rank test was used to compare survival curves and Cox proportional hazard model were used to multivariate analysis. The study cohort included 59 patients with a mean age of 30,83±10,14 years with M:F ratio of 1.68. The mean graft survival was 11.22±4,14 years in the overall cohort. The graft survival rates at 1 ,3, 5, 7 and 10 years were 98,3%,93,2%,89,8%,81,4%and 59,3% respectively. We identified 45 (76 ,3%) patients with a functional graft for 10 or more years after transplantation and 18.6% for 15 or more. In the univariate analyses factors statistically associated to long survival (≥ 10-year) were: recipient age below 35 years (P = 0.016), ABO-identical matching (P = 0.02), higher 3 month (P = 0.01) , one-year (P = 0.01), 5 years (P = 0.02) estimated glomerular filtration rate and no CMV infection after transplantation (P = 0.01). Our experience in renal transplantation survival rates indicate a success rate comparable to those noted in other reports. The renal function at 1-year after transplantation is important for the 10-year survival of kidney transplants. Accordingly, efforts should be targeted to preserving graft function in the first year after kidney transplantation.

Remnant cholesterol is prospectively associated with cardiovascular disease events and all-cause mortality in kidney transplant recipients: the FAVORIT study.

The cholesterol content of circulating triglyceride-rich lipoproteins is characterized as remnant cholesterol, although little is known about its role in the development of cardiovascular disease (CVD) outcomes, all-cause mortality or transplant failure in kidney transplant recipients (KTRs). Our primary aim was to investigate the prospective association of remnant cholesterol and the risk of CVD events in renal transplant recipients with secondary aims evaluating remnant cholesterol and renal graft failure and all-cause mortality among participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial. Among 4110 enrolled participants, 98 were excluded for missing baseline remnant cholesterol levels and covariates. Nonfasting remnant cholesterol levels were calculated based on the lipid profiles in 3812 FAVORIT trial participants at randomization. A Wilcoxon-type test for trend was used to compare baseline characteristics across remnant cholesterol quartiles. Cox proportional hazards regression was used to evaluate the association of baseline remnant cholesterol levels with time to primary and secondary study outcomes. During a median follow-up of 4.0 years we documented 548 CVD incident events, 343 transplant failures and 452 all-cause deaths. When comparing the highest quartile (quartile 4) to quartile 1, proportional hazard modeling revealed a significant increase in CVD risk {hazard ratio [HR] 1.32 [95% confidence interval (CI) 1.04-1.67]} and all-cause mortality risk [HR 1.34 (95% CI 1.01-1.69)]. A nonsignificant increase in transplant failure was seen as well [HR 1.20 (95% CI 0.87-1.64)]. Remnant cholesterol is associated with CVD and all-cause mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of remnant cholesterol-lowering therapy on these outcomes may be warranted.

STABIL-study: The Course of Therapy, Safety and Pharmacokinetic Parameters of Conversion of Prograf® to Tacrolimus HEXAL®/Crilomus® in Renal Transplant Recipients - an Observational Study in Germany.

Tacrolimus HEXAL®/Crilomus® is an approved generic immunosuppressant for the prevention and treatment of rejection following renal transplantation. For safe and socioeconomically efficient conversion of the innovator into a generic formulation, high- -quality data are necessary, in view of the different and country-specific comorbidities and pharmacokinetics in kidney transplant recipients. From 2014 to 2017, we enrolled 32 kidney transplant recipients, receiving newly prescribed Tacrolimus HEXAL®/Crilomus® in 5 German centers. Efficacy and safety data were collected over 6-8 months and retrospectively compared to the period prior to conversion. The mean tacrolimus trough level was 4.91 ng/mL Standard Deviation (SD) (SD ±1.7) before and 5.06 ng/mL (SD ±1.97) after conversion. Mean tacrolimus trough concentration-dose-ratio (+/- SD) was 187.1 ng/mL/mg/kg/day (SD 99.2) for the reference and 205.1 ng/mL/mg/kg/day (SD 133) for the generic product, resulting in a non-significant difference of 18.0 ng/mL/mg/kg/day (SD 71.8) (p=0.84, Wilcoxon V=180). Overall, dosing had to be changed in 4 (14.8%) patients. Graft function remained stable and no rejections occurred. In conclusion, conversion to the generic tacrolimus formulation can be considered safe and feasible in long-term kidney transplant recipients in Germany. As suggested by guidelines, vigilant therapeutic drug monitoring is recommended to account for possible tacrolimus concentration variability on the individual patient level.

Clinical and immunological follow-up of very long-term kidney transplant recipients treated with calcineurin inhibitors indicates dual phenotypes

Operationally tolerant kidney transplant recipients harbor an immunological signature, associated with low rejection risk, and focused on B lymphocytes. Here, we investigated whether patients with long-term transplantation and still on immunosuppressive therapy would present such a signature of low immunological rejection risk, compared to more recently transplanted patients. Of 114 kidney transplant recipients enrolled, 38 with more than 25 years of graft survival and stable graft function under calcineurin inhibitors, were matched with two different groups of transplanted patients (10-15 and 5-7 years after transplantation). Three phenotypes associated with low immunological rejection risk (Tfh, B and regulatory T cells), initially found in operationally tolerant kidney transplant recipients, and the composite score of tolerance (combination of six transcriptomic markers, age at transplantation and age at sampling) were analyzed. We found that very long-term patients were characterized by a significantly lower percentage of total B cells, a significantly higher proportion of CD24HiCD38Lo memory B cells, significantly fewer CD24LoCD38Lo naive B cells, and a significantly lower proportion of PD1HiCCR7Lo Tfh lymphocytes than more recently transplanted patients. This phenotype is associated with a positive composite score of tolerance in patients transplanted for more than 25 years. Thus, our study suggests a dual phenotype in very long-term kidney transplanted patients with an immunological profile associated with low rejection risk.

Microvascular inflammation is a risk factor in kidney transplant recipients with very late conversion from calcineurin inhibitor-based regimens to belatacept

BackgroundIn de novo kidney transplant recipients (KTR) treatment with belatacept has been established as a comparable option as maintenance immunosuppression, preferably as a strategy to convert from calcineurin inhibitor (CNI)- to belatacept-based immunosuppression. Switch to belatacept demonstrated improved renal function in patients with CNI-induced nephrotoxicity, but risk of transplant rejection and the development of donor-specific antibodies (DSA) are still a matter of debate. Only few data are available in patients at increased immunological risk and late after transplantation.MethodsWe analyzed 30 long-term KTR (including 2 combined pancreas-KTR) converted from CNI to belatacept > 60 months after transplantation with moderate to severe graft dysfunction (GFR ≤ 45 mL/min). Biopsies were classified according to the Banff 2015 criteria. Group differences were assessed in a univariate analysis using Mann Whitney U or Chi square test, respectively. Multivariate analysis of risk factors for treatment failure was performed using a binary logistic regression model including significant predictors from univariate analysis. Fifty-six KTR matched for donor and recipient characteristics were used as a control cohort remaining under CNI-treatment.ResultsPatient survival in belatacept cohort at 12/24 months was 96.7%/90%, overall graft survival was 76.7 and 60.0%, while graft survival censored for death was 79.3%/66.7%. In patients with functioning grafts, median GFR improved from 22.5 mL/min to 24.5 mL/min at 24 months. Positivity for DSA at conversion was 46.7%. From univariate analysis of risk factors for graft loss, GFR < 25 mL/min (p = 0.042) and Banff microvascular inflammation (MVI) sum score ≥ 2 (p = 0.023) at conversion were significant at 24 months. In the analysis of risk factors for treatment failure, a MVI sum score ≥ 2 was significant univariately (p = 0.023) and in a bivariate (p = 0.037) logistic regression at 12 months. DSA-positivity was neither associated with graft loss nor treatment failure. The control cohort had comparable graft survival outcomes at 24 months, albeit without increase of mean GFR in patients with functioning grafts (ΔGFR of − 3.6 ± 8.5 mL/min).ConclusionRescue therapy with conversion to belatacept is feasible in patients with worsening renal function, even many years after transplantation. The benefit in patients with MVI and severe GFR impairment remains to be investigated.