Cohort Of Kidney Transplant Recipients Research Articles

MO946: Factors Associated With Changes in Health-Related Quality of Life (Hrqol) in A Greek Cohort of Kidney Transplant Recipients: A Prospective Study

Abstract BACKGROUND AND AIMS Kidney transplantation is recognized as the treatment of choice for patients with End Stage Kidney Disease (ESKD). Improvement in short term patient and graft survival of kidney transplant recipients (KTRs), has shifted interest to the long-term outcomes and Health-Related Quality of Life (HRQoL) estimation is closely related. Thus, reliable evaluation of HRQoL with disease-specific questionnaires is of great importance. The aim of our study was to assess prospectively possible changes in HRQoL during follow up period and to identify associated factors that might affect these changes. METHOD We used the Greek version of the translated and adapted by our team disease-specific instrument Kidney Transplant Questionnaire 25 (KTQ-25) and the Greek SF-36 were administered in a cohort of KTRs during their routine visit in the transplant outpatient clinic twice, at study entry and after one year. Sociodemographic and medical information were also collected at both time points. Inclusion criteria were, aged ≥18-year-old, time since transplant ≥1 year, functioning transplant. All participants provided written informed consent. RESULTS A total of 84 KTRs (59 males; mean age 53.5 ± 10.7; mean e-GFR 47.7 ± 15.1 mL/min/1.73 m2; average time since transplantation 55.7 ± 48.3 months) included in the study at the first time point, while 74 KTRs (88.1%) remained for the second assessment (3 died, 4 denied and 4 changed transplant unit). The majority of KTRs were married (73.8%), with children (77.4%), non-smokers (81.6%) and retired (60.7%). The 45.8% had family monthly income ≤ 1000€. In 62%, hemodialysis was the modality before transplantation and 59.52% had received graft from deceased donor. Immunosuppressive treatment was 84.34% corticosteroids, 54.22% Tacrolimus, 40.96% Cyclosporine, 91.75% MMF and 3.61% Azathioprine. The observed SF-36 scores in all dimensions both time-points were similar without significant changes. Also, no significant changes found between the two time-points at all 5 dimensions and total score of the KTQ-25. A multivariate regression analysis for the 5 dimensions of the KTQ-25 at the second time-point was done. Showed that variables significantly associated with Physical Symptoms dimension was age (P = 0.021) directly and Osteoporosis (P = 0.025) inversely. In regression analysis of Fatigue dimension, variables that remained significant were female sex (P = 0.046) and higher serum cholesterols’ levels (P = 0.012). Uncertainty/Fear dimension was significantly worse in KTRs with history of cardiovascular disease (P = 0.032). Appearance dimension was significantly and positively correlated with female sex and negative with age and history of cardiovascular disease (P = 0.018, P = 0.043 and P = 0.041, respectively). No significantly correlation found for Emotions dimension. Total KTQ-25 score was significantly correlated with female sex (P = 0.024), while history of cardiovascular disease had a negative impact on the score (P = 0.013). CONCLUSION In this one-year prospective study of the HRQoL of KTRs, no statistically significant changes were found in the scores of KTQ-25 and SF-36 instruments. Age, sex, osteoporosis, serum cholesterols’ levels and history of cardiovascular disease are some of the factors that might affect prospectively HRQoL of KTRs.

FC 114: Monoclonal Gammopathy in Kidney Transplanted Patients: Novel Insights into Long-Term Outcomes

Abstract BACKGROUND AND AIMS As in the general population the prevalence of monoclonal gammopathies (MG) in kidney transplant (KT) candidates increases with age. Little is known about the epidemiology and long-term consequences of MG on overall survival, graft outcomes and infectious and neoplastic complications in patients undergoing KT. METHOD We retrospectively identified patients with MG at the time of transplant (KTMG) or appearing de novo after the KT (DNMG) in 3059 patients who underwent a KT from January 2007 to June 2019 at Necker Hospital Paris (N = 1978) and from January 1998 to December 2017 at CHU Poitiers, France (N = 1081). Using a propensity score, we established a control cohort of KTMG from Necker Hospital, matched on the main covariates influencing post KT outcomes. RESULTS We identified 70 (2.3%) KTMG and 114 (3.7%) DNMG patients, presenting with identical demographic characteristics except for an older age in KTMG (62 versus 57 years; P = 0.03). MG isotypes among the 184 KT recipients with MGUS were IgG (n = 117, 64%), IgA (n = 16, 9%) or IgM (n = 16, 9%). Interestingly, DNMG patients presented more frequently with bi- or triclonal MG than KTMG patients (n = 28, 25% versus n = 7, 10%, respectively; P = 0.02). At the time of KT, among 62 patients with available sFLC measurement in KTMG, 11 (17%) had an abnormal kappa/lambda ratio. Because of systematic evaluation of SPEP during follow-up, we observed that MG disappeared during follow up more frequently in DNMG compared to KTMG (n = 51, 45% versus n = 17, 24%, respectively; P = 0.007). Figure 1 represents the results of SPEP during follow-up. FIGURE 1: Monoclonal gammopathy timescale. Serum protein electrophoresis follow-up from KT;each patient is represented by one line. Blueand green lines represent negative SPEP, performed before and after the detection of MG, and red lines represent positive SPEP with MG identification. Clinical last follow-up is represented by dots: red dot for death, blue dot for graft loss and green dot for last follow-up alive with functional graft. Overall survival was poorer in KTMG than in DNMG (87 versus 176 months; P < 0.001). Cox model including age, sex, rank of transplantation and KTMG or DNMG revealed that age, rank of transplantation and KTMG were independent risk factors for death. Graft survival, occurrence of rejection and haematological complications were comparable between the two groups. To better evaluate the effect of MGUS at the time of KT, KTMG patients from Necker Hospital were compared with matched KT recipients. There was no difference between KTMG and controls regarding the main baseline predictors of post-KT outcomes except for lower level of residual gammaglobulins [7.5 g/L (IQR 6–9.9)] in KTMG versus 10.7 g/l (IQR 8.9–13.1) in controls (P < 0.0001). KTMG patients developed more frequently solid cancers (15% versus 5%; P = 0.04) and bacterial infections (63% versus 48%; P = 0.08). There was no significant difference regarding survival, frequency of rejection or haematological complications. However, KTMG patients with an abnormal kappa/lambda ratio at the time of KT tended to have poorer overall survival than those with normal kappa/lambda ratio and controls (respective medians 72, 87 and 103 months; P = 0.08) (Figure 2). CONCLUSION We report here the largest cohort of KT recipients who underwent systematic SPEP screening at the time of KT and yearly during post-transplant follow-up. We observed that MGUS prevalence in KT candidates is close to that reported in the general population. We confirm that outcomes of patients harboring MGUS at the time of KT are similar to those of matched controls without MGUS, supporting that MGUS should not be a contraindication for KT. Nevertheless, we observed that KTMG patients developed more frequently and earlier solid cancers and infections, suggesting that MGUS is associated with a relative immunodeficiency in these patients. We also showed that patients with abnormal sFLC kappa/lambda ratio experienced poor outcomes, claiming for systematic measurement of sFLC in the pre-KT workup. Clinical last follow-up is represented by dots: red dot for death, blue dot for graft loss and green dot for last follow-up alive with functional graft.

MO637: Effectiveness and Safety of Glucagon-Like Peptide-1 Receptor Agonist in a Cohort of Kidney Transplant Recipients

Abstract BACKGROUND AND AIMS Diabetes mellitus (DM) is a complication in kidney transplant (KT). Therapies such as glucagon-like peptide-1 receptor agonist analogs (GLP-1RA) have been incorporated that could have benefits in KT, although experience is limited [1, 2]. The objective of our study is to describe the effectiveness and safety of GLP-1RA in KT patients. METHOD Retrospective cohort study of KT with DM who started GLP-1RA between February 2016 and December 2021. Clinical and demographic variables were analyzed. We collected GLP-1RA type and dose. Glomerular filtration rate (eGFR), proteinuria and weight were collected at the start of treatment and after 6 and 12 months. We analyze glycemic control, blood pressure and lipid profile. Acute rejections (AR), de novo donor-specific antibodies (DSA) and adverse effects were documented. A descriptive analysis was performed and the variables described before and after the start of treatment were compared. Parametric and non-parametric tests were performed according to the normality of the sample. RESULTS In this period, 50 KT with DM treated with GLP-1RA in our center from 1 March 2016 to 15 December 2021. Sixteen patients (32%) had developed post-transplant diabetes mellitus (PTDM). The mean age was 62.8 years and 52.5% were men. Mean baseline estimated glomerular filtration rate (eGFR) was 46.1 mL/min/1.73 m2 and the time post-KT was 38 months. The GLP-1RA mostly prescribed was semaglutide (47.5%), followed by liraglutide (32.5%) and dulaglutide (20%). Twenty-nine patients (58%) reached the maximum recommended dose of the drug. All patients received steroids, tacrolimus and mycophenolate. Forty KT recipients had a minimum follow-up of 6 months and 26 were followed for 12 months. Values of variables compared during the follow-up are shown in Table 1. We observed an improvement in eGFR (+3.5 mL/min/1.73 m2 at 12 months, P = 0.030) and a reduction in proteinuria (−59.1 mg/g at 6 months, P = 0.009 and −48.5 mg/g at 12 months, P = 0.021) during all the follow-up. Additionally, we found a significant reduction in systolic blood pressure (−9.2 mmHg at 12 months, P = 0.022) despite the number of patients receiving angiotensin receptor blockers, angiotensin-converting enzyme and other antihypertensive therapies as well as their doses that did not change during the period of the study. In our cohort, body weight significantly reduced (−2.4 Kg at 6 months, P = 0.006 and −3 Kg at 12 months, P = 0.041). Furthermore, HbA1c decreased (−9 mmol/mol at 6 months, P <0.001 and −5 mmol/mol at 12 months, P = 0.018). Notably, insulin dose was also reduced (−4 UI/day at 6 months, P = 0.003 and −4 UI/day at 12 months, P = 0.036) and the rest of antidiabetic treatment did not significantly change. Finally, we observed a reduction in total cholesterol (−14 mg/dL at 6 months, P = 0.015 and −6.3 mg/dL at 12 months, P = 0.344) and LDL-c (−8.8 mg/dL at 6 months, P = 0.49 and −4.9 mg/dL at 12 months, P = 0.384) during the follow-up. Twelve patients (24%) suffered from side effects, mainly nausea and vomiting, and only two patients (4%) discontinued the treatment. One patient discontinued the treatment due to the diagnosis of pancreatic cancer 8 months after starting the drug. We did not find differences in the levels or in the dose of tacrolimus. Neither AR episodes nor de novo DSAs’ development was notified. CONCLUSION In conclusion, this is one of the largest series reporting the effectiveness and safety of GLP-1RA in a cohort of KT. Our results support that it can be an option for the management of DM in these patients. Its use is safe and it does not seem to alter tacrolimus trough levels, to induce AR episodes or de novo DSAs development.

MO941: Novel Peripheral Molecular Markers Predict Premature Graft Loss: Lessons Learned from Operational Tolerance Assessment

Abstract BACKGROUND AND AIMS TOMOGRAM, a European multicenter study, recently identified a new cohort of kidney transplant recipients (KTR) with operational tolerance (OT) with the aim to identify new transcriptomic signatures of OT. METHOD RNA sequencing of peripheral blood was evaluated in 15 OT KTR identified by TOMOGRAM, 23 stable KTR (≥15 years, STA), 14 KTR with transplant glomerulopathy (≥1 year, CR), 14 CyA-treated primary GN patients and 14 healthy controls (HC). The ability to discriminate OT from others was analyzed using three classifiers (GLMNET, voomNSC and SVM-RFE) with 10-fold cross-validation and visualized by principal component analysis (PCA) of molecular archetypes. RESULTS Peripheral blood transcriptome of OT patients is similar to the STA group (AUC < 0.6) and different from the CR group (AUC > 0.8). Also, in PCA of molecular archetypes, direction of correlation suggested similarity between STA and OT and their anti-correlation to CR (Figure 1). Top 10 transcripts differentiated OT from CR were assessed in prospective independent cohort (n = 396) to predict premature graft loss. Multivariable Cox regression model based on the expression of 5 of those transcripts at 3 time-points was associated with graft loss at 3 years with an AUC = 0.815. CONCLUSION Identification of the OT peripheral molecular signature among stable KTR is not feasible. Instead, novel peripheral molecular markers associated with premature graft loss were identified.

MO955: Serum Cystatin C in Renal Transplantation: Beyond GFR Estimation, A Prognosis Marker?

Abstract BACKGROUND AND AIMS In renal transplantation, death with a functioning graft remains one of the main causes of graft loss. In the general population, renal function impairment is strongly associated with cardiovascular and all-cause mortality. Whether this association holds true for kidney transplant recipients (KTR) is unclear. This uncertainty is likely to be due, in part, to the fact that glomerular filtration rate (GFR) estimation based on serum creatinine (SCr) does not always provide an accurate evaluation of the graft function in KTR. As compared to SCr, we have previously shown in a large cohort of KTR that serum cystatin C (SCysC) is a much better marker of GFR. Herein, we sought to study the ability of the 1-year-post-transplant renal function to predict all-cause mortality according to the methods used to assess GFR. METHOD Four hundred and ten consecutive KTR for whom a measurement of GFR by inulin clearance was available at 1 year post-transplant were included. SCr and ScysC were measured with standardized methods. The association of the 1-year inulin clearance value the 1-year MDRD Study equation value and the 1-year CKD-EPI ScysC equation value with all-cause mortality was studied by ROC analysis and Cox model. RESULTS During a median follow-up of 17 years, 131 KTR died. Mean (±SD) inulin clearance at 1-year-post-transplant was 47 (±13) mL/min/1.73 m2. Areas under the ROC curves were similar for inulin and CKD-EPI ScysC equation values (0.62 for both), and were both significantly superior to that of the MDRD equation (0.54, P < 0.01). In Cox analysis, while all types of GFR evaluations were significantly associated to graft loss, only an inulin and a CKD-EPI ScysC equation values below 45 mL/min/1.73 m2 were associated with an excess risk of mortality (HR of 1.55, 1.45 and 1.01 for inulin, CKD-EPI ScysC and MDRD, respectively). CONCLUSION We conclude that ScysC-based GFR estimation might better predict KTR outcome as compared with a traditional SCr-based estimation. The one year-post transplant GFR value given by the CKD-EPI ScysC equation should be further evaluated as a potential surrogate marker for both graft and patient survival.

Pathways from Diagnosis to Death from Keratinocyte Cancer in Kidney Transplant Recipients

Background: Kidney transplant recipients are at increased risk of developing and dying from keratinocyte cancer. We aimed to describe the clinical course of keratinocyte cancer-related deaths in a cohort of kidney transplant recipients. Methods: In kidney transplant recipients transplanted between 1995 and 2014 in Queensland, Australia, we ascertained keratinocyte cancer deaths by searching national transplant and state death registries to March 2020. Deceased transplant recipients’ medical records were reviewed to assess features of the primary lesion of the fatal keratinocyte cancer, metastases, and clinical information before death. Results: Of 658 kidney transplant recipient deaths, 49 (7%) were due to keratinocyte cancer, and medical records were available for 36 (73%). One death was due to basal cell carcinoma, and 35 were from squamous cell carcinoma (SCC), primarily from the head and neck (24; 69%). The most common site of metastasis was the lungs (21; 58%). Median time (minimum, maximum) from the diagnosis of primary SCC to metastasis was 5 months (0, 29). After this, the median time to death was 9 months (1, 50). Conclusion: Fatal keratinocyte cancers overwhelmingly arise on the head and neck, with lungs the most common metastasis site. The short time from diagnosis of primary to death indicates the aggressive nature of these keratinocyte cancers.

Radiofrequency Echographic Multi-Spectrometry (REMS) technology and DXA for BMD assessment in kidney transplant recipients

Radiofrequency Echographic Multi-Spectrometry (REMS) is a novel ultrasound-based technique that has shown good reliability in the assessment of BMD in women affected by post-menopausal osteoporosis. Data on special populations with secondary osteoporosis are needed. The aim of this study was to compare the performance of the REMS BMD assessment with DXA in a cohort of kidney transplant recipients (KTR). Consecutive patients referring to our KTR clinic were enrolled. All subjects fulfilled the following inclusion criteria: Caucasian population, both genders, age between 40 and 80 years, BMI < 40kg/m2. The enrolled patients underwent a lumbar spine (LS) and femoral neck (FN) examination with DXA and REMS. Differences in DXA vs REMS T-scores were analyzed through Student's t test for independent samples, correlations were tested though Pearson's correlation. Differences in prevalence were tested trough Chi-squared test. Written informed consent was obtained from all participants (protocol 1483CESC). 40 patients were enrolled (table 1). At the LS, BMD was significantly lower when assessed through REMS. The correlation between the T-scores obtained with DXA and REMS are depicted in figure 1. When adopting the worst site, the prevalence of subjects with T-score <-2.5 was 40.5% with DXA and 37.8% with REMS (p=NS) and of subjects with T-score <-1 was 89% with DXA and 97.5% with REMS (p=0.003). These results showed a good reliability of the REMS technology with respect to DXA in the classification of KTR patients as having low bone mass and/or osteoporosis. Furthermore, REMS might be more sensitive than DXA in the detection of early bone impairment and in the classification of KTR patients with low bone mass. Uploaded File(s)

De Novo Membranous Nephropathy Associated With Antibody-Mediated Rejection in Kidney Transplant Recipients

Membranous nephropathy (MN) is a rare autoimmune disease that can develop a persistent nephrotic syndrome and end-stage kidney disease, with a recurrence rate of 30% to 40% after kidney transplant. Retrospective case series of membranous nephropathy observed in a cohort of kidney transplant recipients with donor-specific anti-human leukocyte antigen antibodies and biopsy-proven antibody-mediated rejection (AMR). We report 4 cases of membranous nephropathy associated with AMR. MN was diagnosed 10 to 92 months posttransplant, associated with de novo donor-specific antibodies, specific to class I in 2 cases, and class II in another 2. All cases presented typical morphology of membranous nephropathy, with subepithelial deposits with spikes at electron microscopy. Immunostaining for immunoglobulin G4 was negative in all cases, and podocyte-expressed M-type phospholipase A2 receptor was detected in glomerular basement membrane of 3 cases. Biopsy specimens from patients with longer follow-up showed more intense microvascular inflammation and chronic injury markers, possibly because of subclinical immunologic injury. AMR therapy included immunoglobulin 2g/kg in 3 patients, isolated or associated with plasmapheresis. One patient was not treated because of an active disseminated infection. Two patients remain with functioning grafts and under antiproteinuric therapy. Two grafts were lost, 1 because of chronic failure and the other because of death secondary to infection. Despite treatment, donor-specific antibodies remain detectable in a 6-month follow-up. De novo MN is a rare manifestation associated with AMR in kidney transplant recipients. The occurrence of podocyte-expressed M-type phospholipase A2 receptor in de novo MN suggests antibody-mediated activation, despite the use of maintenance immunosuppression.

Pregnancy Outcomes After Kidney Transplantation and Long-Term Evolution of Children: A Single Center Experience

Pregnancies in women who underwent kidney transplants are at high risk compared with the general population. In this study, we aimed to retrospectively assess the obstetrical complications, delivery outcomes, and impact of pregnancy on kidney allograft function in a single-center cohort of kidney transplant recipients (KTRs). We provide data regarding the long-term evolution of children. Thirty-two KTRs underwent a total of 57 pregnancies between 1994 and 2010. Fourteen pregnancies (24 %) did not survive caused by miscarriages (n=9), stillborn (n=1), ectopic pregnancies (n=2), and medical abortion (n=2). Live birth occurred in 76% of pregnancies. Delivery was by cesarean in 66%. The mean gestational age was 30.45 ± 11.3 weeks and 65% of newborns were premature. A low birth weight <2500g was noted in 46%. Obstetric complications were de novo hypertension in 4%, pre-eclampsia in 9%, and gestational diabetes in 2%. The 5- and 10-year post-delivery death-censored graft loss rates were 3.1% and 12.5%, respectively. Data on 21 children were collected via a self-questionnaire. After a median follow-up time of 17 years, they appeared in good medical and psychological health. None of them suffered from chronic disease (especially uronephrological condition) or was taking chronic medication. Long-term evolution of children born to women who underwent kidney transplants seems favorable. Pregnancies in KTRs are successful in two-thirds of cases but are at increased risk of prematurity, delivery by cesarean, and low birth weight.

SARS-CoV-2 antibody dynamics among kidney transplant recipients 3 months after BNT162b2 vaccination: a prospective cohort study.

ABSTRACTData regarding immunogenicity of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among kidney transplant recipients in the months following vaccination are lacking. We aimed to investigate humoral immune response at 3–4 months post-vaccination among a cohort of kidney transplant recipients, compared with a control group of dialysis patients. Anti-spike antibodies were tested at 1 and 3–4 months after vaccination. Of 259 kidney transplant recipients tested at a median time of 110 days from second vaccine dose, 99 (38%) were seropositive, compared with 83% (101/122) of control patients. Younger age, better renal function and lower immunosuppression levels were associated with seropositivity. A total of 14% (13/94) of participants seropositive at 1 month became seronegative at follow-up and 11% (18/165) became seropositive. The latter were mainly individuals with higher antibody levels at 1 month. Antibody levels at 3–4 months were significantly reduced in both study groups, although the decline was more pronounced in the control group. Kidney transplant recipients present poor antibody response to mRNA SARS-CoV-2 vaccination, with only 38% seropositive at 3–4 months. Nevertheless, the decay in antibody response over time is modest, and some patients may present delayed response, reaching adequate antibody levels at 3–4 months. Low seropositivity rates in this group call for investigating other immunization strategies.

An Antibody-Aptamer-Hybrid Lateral Flow Assay for Detection of CXCL9 in Antibody-Mediated Rejection after Kidney Transplantation.

Chronic antibody-mediated rejection (AMR) is a key limiting factor for the clinical outcome of a kidney transplantation (Ktx), where early diagnosis and therapeutic intervention is needed. This study describes the identification of the biomarker CXC-motif chemokine ligand (CXCL) 9 as an indicator for AMR and presents a new aptamer-antibody-hybrid lateral flow assay (hybrid-LFA) for detection in urine. Biomarker evaluation included two independent cohorts of kidney transplant recipients (KTRs) from a protocol biopsy program and used subgroup comparisons according to BANFF-classifications. Plasma, urine and biopsy lysate samples were analyzed with a Luminex-based multiplex assay. The CXCL9-specific hybrid-LFA was developed based upon a specific rat antibody immobilized on a nitrocellulose-membrane and the coupling of a CXCL9-binding aptamer to gold nanoparticles. LFA performance was assessed according to receiver operating characteristic (ROC) analysis. Among 15 high-scored biomarkers according to a neural network analysis, significantly higher levels of CXCL9 were found in plasma and urine and biopsy lysates of KTRs with biopsy-proven AMR. The newly developed hybrid-LFA reached a sensitivity and specificity of 71% and an AUC of 0.79 for CXCL9. This point-of-care-test (POCT) improves early diagnosis-making in AMR after Ktx, especially in KTRs with undetermined status of donor-specific HLA-antibodies.

Humoral and T-cell response to SARS-CoV-2 mRNA BNT162b2 vaccination in a cohort of kidney transplant recipients and their cohabitant living kidney donor partners.

Humoral and T-cell response to SARS-CoV-2 mRNA BNT162b2 vaccination in a cohort of kidney transplant recipients and their cohabitant living kidney donor partners.

SARS-CoV-2 infection in kidney transplant recipients: clinical impact and outcomes - a single center experience.

ABSTRACTIntroduction:Kidney transplant recipients are a subgroup of patients at higher risk of critical forms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and poor outcomes due to immunosuppression treatment. Herein, we present data from a single center cohort of kidney transplant recipients with SARS-CoV-2 infection.Methods:In a prospective study, baseline characteristics, clinical features, antiviral and immunosuppression management were compared between outpatients and hospitalized patients, during a one-year period.Results:Seventy-seven kidney transplant recipients were analyzed, including outpatients and hospitalized patients, with a median age of 57.7 (IQR 49.7-64.9) years. Twenty-eight (36.4%) were managed as outpatients, while 49 (63.6%) patients required hospital admission. Among hospitalized patients, 18.4% were admitted in ICU, 49% had AKI, and 20.4% died. Immunosuppression adjustments were performed in 95.9% of hospitalized patients, with dose of anti-metabolites adjusted in 83.7%, mTOR inhibitors in 14.3%, calcineurin inhibitors in 12.2%, and corticosteroid therapy in 81.6%.Conclusion:Among hospitalized patients, immunosuppression management included reduction or withdrawal of anti-metabolite and increase of corticosteroid dose. AKI occurred in almost half of patients and mortality in hospitalized patients reached 20%, reflecting greater disease severity than the general population.

Effect of pulmonary hypertension on 5-year outcome of kidney transplantation.

Pulmonary hypertension affects about one in four patients with advanced chronic kidney disease and significantly increases the risk of death. Kidney transplantation is the recommended management option for patients with progressive or end‐stage kidney disease. However, the resource‐limited nature of kidney transplantation and its intensive peri‐operative and posttransplantation management motivates careful consideration of potential candidates’ medical conditions to optimally utilize available graft organs. Since pulmonary hypertension is known to increase peri‐operative morbidity and mortality among patients living with chronic kidney disease, we performed a retrospective cohort study to assess the impact of pretransplantation pulmonary hypertension on posttransplantation outcome. All patients who underwent single‐organ kidney transplantation at our center in calendar years 2010 and 2011 were identified and the presence of pulmonary hypertension was determined from pretransplantation echocardiography. Outcome was assessed at 5 years following kidney transplantation. Of 350 patients who were included, 117 (33%) had evidence of pulmonary hypertension. The risk of death, graft dysfunction, or graft failure at 5 years after kidney transplantation was higher among those with pulmonary hypertension, primarily owing to an increased risk of graft dysfunction. Importantly, in this institutional cohort of kidney transplant recipients, pretransplant pulmonary hypertension was not associated with a difference in posttransplant survival at 5 years. While institutional and regional differences in outcome can be expected, this report suggests that carefully selected patients with pulmonary hypertension receive similar long‐term benefits from kidney transplantation.

Association of endothelial dysfunction with sarcopenia and muscle function in a relatively young cohort of kidney transplant recipients.

BackgroundSarcopenia and endothelial dysfunction are both common among kidney transplant (KT) recipients. We aimed to evaluate the association between endothelial dysfunction and sarcopenia, as well as its individual components.MethodsVascular reactivity index (VRI), skeletal muscle index (SMI = skeletal muscle mass/height2), handgrip strength (HGS), and 6-meter usual gait speed (GS) were measured in 95 KT recipients. Low SMI was defined as SMI less than 10% of the sex-specific reference values from Chinese adults; low HGS as HGS < 28 kg for men and < 18 kg for women; slow GS as GS below 1.0 m/s. Sarcopenia was diagnosed based on the presence of low SMI as an essential criterion, accompanied by either low HGS or slow GS. Vascular reactivity was classified as being indicative of poor (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), or good (VRI ≥ 2.0) vascular reactivity.ResultsOf the 95 patients, aged 45.2 ± 10.9 years, 11.6% had sarcopenia and 13.7% had poor vascular reactivity. Patients with sarcopenia were lower in body mass index (p = 0.001) and VRI (p = 0.041), and have a higher proportion of low muscle mass (p < 0.001), low HGS (p < 0.001), and slow GS (p = 0.001). Patients with poor vascular reactivity have a higher proportion of sarcopenia (p = 0.005), low HGS (p = 0.006), and slow GS (p = 0.029). Multivariate logistic regression analysis showed that patients in the poor VRI group were significantly associated with sarcopenia (odds ratio, OR = 6.17; 95% confidence interval [1.06–36.04]; p = 0.043), comparing to those with good VRI. We further analysed the effects of VRI on individual components of sarcopenia and found that VRI predicted slow GS significantly (OR = 0.41; 95% CI = [0.21–0.79]; p = 0.007), but not low SMI (OR = 1.15; 95% CI [0.53–2.49]; p = 0.718) and HGS (OR = 0.59; 95% CI [0.31–1.16]; p = 0.125).ConclusionsWe concluded that endothelial dysfunction is a key determinant of sarcopenia in KT recipients. Furthermore, endothelial dysfunction is more closely related to gait speed than muscle mass and strength.

Maternal, Decidual, and Neonatal Lymphocyte Composition Is Affected in Pregnant Kidney Transplant Recipients.

Pregnancy after renal transplantation is associated with an increased risk of complications. While a delicately balanced uterine immune system is essential for a successful pregnancy, little is known about the uterine immune environment of pregnant kidney transplant recipients. Moreover, children born to kidney transplant recipients are exposed in utero to immunosuppressive drugs, with possible consequences for neonatal outcomes. Here, we defined the effects of kidney transplantation on the immune cell composition during pregnancy with a cohort of kidney transplant recipients as well as healthy controls with uncomplicated pregnancies. Maternal immune cells from peripheral blood were collected during pregnancy as well as from decidua and cord blood obtained after delivery. Multiparameter flow cytometry was used to identify and characterize populations of cells. While systemic immune cell frequencies were altered in kidney transplant patients, immune cell dynamics over the course of pregnancy were largely similar to healthy women. In the decidua of women with a kidney transplant, we observed a decreased frequency of HLA-DR+ Treg, particularly in those treated with tacrolimus versus those that were treated with azathioprine next to tacrolimus, or with azathioprine alone. In addition, both the innate and adaptive neonatal immune system of children born to kidney transplant recipients was significantly altered compared to neonates born from uncomplicated pregnancies. Overall, our findings indicate a significant and distinct impact on the maternal systemic, uterine, and neonatal immune cell composition in pregnant kidney transplant recipients, which could have important consequences for the incidence of pregnancy complications, treatment decisions, and the offspring’s health.

Longitudinal Assessment of Electrolyte Disorders in a Cohort of Chronic Stable Kidney Transplant Recipients

Kidney transplantation is complicated by various electrolyte disturbances with variable reported prevalence and incidence and of multifactorial pathogenesis. The aim of our study was the retrospective longitudinal assessment of the serum electrolytes in a cohort of stable kidney transplant recipients (KTRs) and the possible associated parameters, including graft function and medications. We included 93 stable KTRs under follow-up in our hospital's kidney transplant unit. Serum magnesium, calcium, phosphorus, potassium, sodium, and urine sodium levels were recorded retrospectively during 3 consecutive years. In addition, comorbidities, biochemical parameters, medications, and graft function (estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation and 24-hour urinary protein [uTpr]) were recorded. Mean age at baseline was 51 ± 11 years; 64 KTRs were men (68.8%), 17 (18.3%) had diabetes, 79 (85%) had hypertension, and 11 (11.8%) had cardiovascular disease. Mean eGFR and uTpr (mg/24 h) at study initiation were 47.1 ± 13.5 mL/min/1.73 m2 and 369.4 ± 404.2 mg/24 h, respectively. Hypomagnesemia was the most common disturbance observed in 21.7% of KTRs. Patients with hypomagnesemia displayed higher parathyroid hormone levels and more frequently had diabetes. Hypophosphatemia was recorded in 9.7% of KTRs during the first year. Hyperkalemia, hypokalemia, and hypercalcemia were rare (<5%). Mean serum and urine sodium concentration remained stable during the study, whereas urinary sodium levels showed a positive correlation with uTpr (P < .05). In our cohort of KTRs, there were no significant electrolyte disorders, either in terms of frequency or severity, with hypomagnesemia being the most prevalent disturbance. The identification of potential associated risk factors and clinical data correlations are pivotal for the development of individualized and evidence-based therapeutic approach and decisions.

Correlation of Glomerular Size With Donor-Recipient Factors and With Response to Injury.

Glomerular size in renal allografts is impacted by donor-recipient factors and response to injury. In serial biopsies of patients with well-functioning grafts, increased glomerular size correlates with better survival. However, no previous study has addressed the association of glomerular size at the time of a for-cause biopsy and clinical/histopathologic markers of injury, or effect on long-term graft outcome. Two cohorts of kidney transplant recipients enrolled in the Deterioration of Kidney Allograft Function study were evaluated. The prospective cohort (PC, n = 581): patients undergoing first for-cause kidney biopsy 1.7 ± 1.4 (mean ± SD) y posttransplant; and the cross-sectional cohort (CSC, n = 446): patients developing new-onset renal function deterioration 7.7 ± 5.6 y posttransplant. Glomerular planar surface area and diameter were measured on all glomeruli containing a vascular pole. Kidney biopsy was read centrally in a blinded fashion according to the Banff criteria. Glomerular area was significantly higher in the CSC than the PC; time from transplant to indication biopsy was associated with glomerular area in both cohorts (P values ≤ 0.001). Glomerular area was associated with indices of microvascular inflammation (glomerulitis, peritubular capillary infiltrates; P values ≤ 0.001) and segmental glomerulosclerosis (P value < 0.0001). In the CSC, higher glomerular area was associated with higher estimated glomerular filtration rate (P value ≤ 0.001) and increased graft survival after accounting for microvascular inflammation (adjusted hazard ratio = 0.967; 95% confidence interval: 0.948-0.986; hazard ratio in biopsies without evidence of diabetes or antibody mediated rejection = 0.919, 95% confidence interval: 0.856-0.987). Glomerular size is associated with histopathologic features present at the time of indication biopsy and with increased graft survival in the CSC.

Pregnancy, Contraception, and Menopause in Advanced Chronic Kidney Disease and Kidney Transplant.

Background: Reproductive health is an essential part of the care of women with kidney disease. However, the self-reported patient experience of reproductive issues has been underexplored.Materials and Methods: We identified a cohort of women ages 18 to 44 at the time of kidney transplant from 1996 to 2014 at our 3-site program (n = 816). We sent each woman a survey on her reproductive lifespan, characterizing features from menarche to menopause.Results: We received survey responses from 190 patients (27%). One third of respondents reported amenorrhea before transplant, and 61.5% of these women reported resumption of menses post-transplant. The average age of menopause was 45.5 years, earlier than the general population (51.3 years). There were 204 pregnancies pretransplant and 52 pregnancies post-transplant. Pregnancies post-transplant were more likely to be complicated by preeclampsia, preterm delivery, and small for gestational age babies than pregnancies that occurred >5 years before transplant. Pregnancies <5 years before transplant were similar to post-transplant pregnancies with respect to complications. Forty-two percent of women were advised to avoid pregnancy after transplant, most often by a nephrology provider.Conclusions: In our cohort of kidney transplant recipients, women report increased pregnancy-related complications post-transplant and in the 5 years before transplant, compared with pregnancies that occurred greater than 5 years before transplant. They were often counseled to avoid pregnancy altogether. Women reported a younger age of menopause relative to the general population. This should be considered when counseling patients with chronic kidney disease regarding optimal pregnancy timing.

B-cell activating factor BAFF as a novel alert marker for the immunological risk stratification after kidney transplantation

The B cell activating factor BAFF has gained importance in the context of kidney transplantation due to its role in B cell survival. Studies have shown that BAFF correlates with an increased incidence of antibody-mediated rejection and the development of donor-specific antibodies. In this study, we analyzed a defined cohort of kidney transplant recipients who were treated with standardized immunosuppressive regimens according to their immunological risk profile. The aim was to add BAFF as an awareness marker in the course after transplantation to consider patient’s individual immunological risk profile. Included patients were transplanted between 2016 and 2018. Baseline data, graft function, the occurrence of rejection episodes, signs of microvascular infiltration, and DSA kinetics were recorded over 3 years. BAFF levels were determined 14 d, 3 and 12 months post transplantation. Although no difference in graft function could be observed, medium-risk patients showed a clear dynamic in their BAFF levels with low levels shortly after transplantation and an increase in values of 123% over the course of 1 year. Patients with high BAFF values were more susceptible to rejection, especially antibody-mediated rejection and displayed intensified microvascular inflammation; the combination of high BAFF + DSA puts patients at risk. The changing BAFF kinetics of the medium risk group as well as the increased occurrence of rejections at high BAFF values enables BAFF to be seen as an awareness factor. To compensate the changing immunological risk, a switch from a weaker induction therapy to an intensified maintenance therapy is required.