Function In Kidney Transplant Recipients Research Articles

Reducing Tacrolimus Levels to Improve Cognitive Function in Kidney Transplant Recipients.

Reducing Tacrolimus Levels to Improve Cognitive Function in Kidney Transplant Recipients.

Interactions of TTV with BKV, CMV, EBV, and HHV-6A and their impact on post-transplant graft function in kidney transplant recipients.

Mono and combined reactivation of latent viruses occurs frequently under immunosuppressive therapy in kidney transplant patients. Recently, monitoring torque teno virus (TTV) reactivation came more into focus as a potential biomarker for immune status. The surrogate characteristics of TTV reactivation on acute rejection, and the combined reactivation with other latent viruses such as cytomegalovirus (CMV), human BK virus (BKV), Epstein-Barr virus (EBV), and human herpes virus-6A (HHV-6A) on allograft function, are unknown so far. Blood samples from 93 kidney transplant recipients obtained during the first post-transplant year were analyzed for TTV/BKV/CMV/EBV/HHV-6A load. Clinical characteristics, including graft function [glomerular filtration rate (GFR)], were collected in parallel. TTV had the highest prevalence and viral loads at 100% and a mean of 5.72 copies/ml (cp/ml) (log10). We found 28.0%, 26.9%, 7.5%, and 51.6% of simultaneous reactivation of TTV with BKV, CMV, EBV, and HHV-6, respectively. These combined reactivations were not associated with a significantly reduced estimated GFR at month 12. Of interest, patients with lower TTV loads <5.0 cp/ml (log10) demonstrated not only a higher incidence of acute rejection, but also an unexpected significantly earlier occurrence and higher incidence of BKV and HHV-6A reactivation. Correlations between TTV loads, other latent viruses, and immunosuppressive medication were only significant from 6 months after transplant. We were able to observe and support previously introduced TTV load thresholds predicting kidney allograft rejection. However, due to a possible delayed relation between immunosuppressive medication and TTV viral load adaptation, the right time points to start using TTV as a biomarker might need to be further clarified by other and better designed studies.

#1985 Tocilizumab in chronic active antibody-mediated rejection: a randomized controlled open-label multi-center trial (INTERCEPT study)

Abstract Background and Aims Chronic active antibody mediated graft rejection (caAMR) caused by immune-mediated injury is the leading cause of long-term graft loss in kidney transplant recipients. Nevertheless, no effective treatment exists for caAMR to date, highlighting a great unmet need for evaluation of novel treatment options. Recently, tocilizumab (TCZ), a monoclonal antibody directed against the human interleukin-6 (IL-6) receptor, by antagonizing IL-6-triggered inflammation and B cell/plasma cell-driven immune activation, has shown promise in the treatment of caAMR. However, TCZ has not been assessed systematically in a randomized study. The INTERCEPT study aims to evaluate the efficacy of addition of TCZ to standard of treatment (SOC) as compared to SOC alone in reducing the decline of graft function from baseline at 24 months after start of treatment as assessed by estimated glomerular filtration rate (eGFR) in kidney transplant recipients with caAMR. Method This ongoing randomized controlled open-label multi-center investigator-initiated trial plans to include a total of 50 adult kidney transplant recipients with biopsy-proven caAMR using Banff 2019 criteria at least 12 months after transplantation and eGFR ≥20 ml/min/1.73 m2. Any subject who underwent kidney transplantation in Sweden or is currently living in Sweden and being followed up at any of the Swedish transplant centers or their affiliated regional centers can be considered for participation. Participants are randomized to receive either TCZ (n=25) added to our standard of care (SOC) maintenance treatment or SOC alone (n=25) for a period of 24 months and followed for additional 12 months after cessation of the study medication. After the inclusion transplant biopsy at baseline, protocol biopsies are performed at 12 and 24 months. The study design flow-chart is shown in the Figure. The primary endpoint is the slope of eGFR at 24 months after start of treatment. The eGFR is assessed using Modification of Diet in Renal Disease (MDRD) formula. The secondary endpoints include assessment of the following at 12, 24 and 36 months: composite risk score iBox, safety, evolution and characteristics of donor-specific antibodies (DSA), graft histology, proteinuria, kidney function assessed by measured GFR (mGFR), patient- and death-censored graft survival, patient-reported outcomes that include transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection. Results We expect that addition of TCZ to SOC will slow down the decline of graft function in kidney transplant recipients with caAMR. Conclusion Currently there is no effective treatment for caAMR. Based on the hypothesis that inhibition of IL-6 by TCZ will reduce antibody production and reduce antibody-mediated damage, our randomized trial has a potential to provide evidence for a novel treatment strategy for caAMR. If TCZ is found to be effective, our study has the potential to improve long-term graft survival and quality of life, reduce morbidity and mortality in kidney transplant patients as well as lower the health care costs.

#580 Pitfalls in valganciclovir prophylaxis dose adjustment based on renal function in kidney transplant recipients

Abstract Background Clinically significant cytomegalovirus infection (csCMVi) is the most frequent viral infection in kidney transplant recipients (KTR). A daily dose of 900 mg valganciclovir (VGC) as primary antiviral prophylaxis (PAP) is frequently administered to KTR at risk for csCMVi, including CMV donor (D)+/recipient (R)− and CMV R+ patients after induction immunosuppression with thymoglobulin (R+/TG) until 6- and 3-months post-transplant, respectively. Dose adjustments for VGC are recommended based on renal function to reduce potential myelotoxicity. There is paucity of real-life data on VGC dose adjustment as PAP and association with clinical outcomes. Method and Aims Bicentric and retrospective Swiss Transplant Cohort Study (STCS)-embedded observational study including all consecutive adult D+/R− and R+/TG KTR between 2010 and 2020, who received PAP with VGC. The primary objective was to describe the proportion of VGC weekly entries, that was inappropriately (either under- or over-) dosed based on the associated renal function. Secondary objectives included the incidence of breakthrough csCMVi, potential associations between breakthrough-csCMVi and cytopenias with VGC dosing. Results Among 178 KTR included in both centres, 131 (73.6%) patients had at least two week entries for the longitudinal data of interest and were included in the outcome analysis. There were 1032 weekly VGC dose entries for 131 patients. Overall, 460 (44.6%) were appropriately dosed, while 234 (22.7%) and 338 (32.8%) were under- and over-dosed, respectively (Table 1). Inappropriate dosing was more frequent among R+/TG (133/214, 62.1%) than D+/R− (92/176, 52.3%, p = 0.05) during the first four weeks post-transplant. Nineteen (14.5%) patients had a breakthrough-csCMVi, without any association between breakthrough-csCMVi and VCG dosing (p = 0.44). Among cytopenias, there was no statistically significant difference in the proportion of weekly leucopenia, neutropenia, or thrombocytopenia values. In contrast, lymphopenia was more frequently observed when VGC was overdosed (p = 0.005, Table 2). Conclusion VGC as PAP in KTR is frequently inappropriately dosed, albeit without meaningful clinical associations, neither in terms of efficacy nor safety.

#701 Occult hepatitis B infection in kidney transplant recipients and their donors

Abstract Background and Aims Occult hepatitis B infection (occult HBV infection—OBI) in kidney transplant recipients (KTRs) poses a potential risk of transforming into an overt process during immunosuppressive therapy. We aimed to evaluate the frequency of OBI occurrence in KTRs population and in the corresponding cohort of kidney donors. Method We analyzed 1222 consecutive KTRs transplanted between Jan 2012 and Jun 2023 and their 670 deceased donors. The diagnosis of seropositive OBI was based on the presence of anti-HBc antibodies without detectable HBs antigen. In eligible KTRs with pre-transplant OBI, the status of HBV infection was examined including the HBV-DNA and calculated aspartate aminotransferase to platelet ratio index (APRI) and Fibrosis-4 (FIB-4) indexes to assess the degree of liver fibrosis. Results Prior to transplantation, OBI was diagnosed in 178 (14.9%) KTRs [median age 49 (IQR, 38-59) years] and in 72 (10.7%) donors [median age 49 (38-58)]. OBI was significantly more frequent in KTRs than in general population (χ2=6.4, p&amp;lt;0.05). In a long-term follow-up period [median 84 (47-117) months], 5 out of 85 pre-transplant OBI patients (5.9%) presented the negative HBc status, whereas HBV viremia and HBs antigen, as determined using the high-sensitive method, were absent in all subjects. Among 85 pre-transplant OBI subjects, anti-HBs antibodies &amp;gt;10 mIU/ml were present in 84.7% and no liver fibrosis was found by APRI and FIB-4 indexes calculation. Conclusion 1. OBI is still a significant clinical problem not only in KTRs, but also in the general population, despite the widespread access to preventive vaccinations against HBV. 2. A separate analysis is necessary to evaluate the influence of OBI on kidney graft and liver function in KTRs.

Plasma Symmetric Dimethylarginine and Kidney Graft Function in Kidney Transplant Recipients.

Plasma Symmetric Dimethylarginine and Kidney Graft Function in Kidney Transplant Recipients.

Pitfalls in Valganciclovir Prophylaxis Dose Adjustment Based on Renal Function in Kidney Transplant Recipients.

Valganciclovir (VGC) is administered as prophylaxis to kidney transplant recipients (KTR) CMV donor (D)+/recipient (R)- and CMV R+ after thymoglobulin-induction (R+/TG). Although VGC dose adjustments based on renal function are recommended, there is paucity of real-life data on VGC dosing and associations with clinical outcomes. This is a retrospective Swiss Transplant Cohort Study-embedded observational study, including all adult D+/R- and R+/TG KTR between 2010 and 2020, who received prophylaxis with VGC. The primary objective was to describe the proportion of inappropriately (under- or over-) dosed VGC week-entries. Secondary objectives included breakthrough clinically significant CMV infection (csCMVi) and potential associations between breakthrough-csCMVi and cytopenias with VGC dosing. Among 178 KTR, 131 (73.6%) patients had ≥2week-entries for the longitudinal data of interest and were included in the outcome analysis, with 1,032 VGC dose week-entries. Overall, 460/1,032 (44.6%) were appropriately dosed, while 234/1,032 (22.7%) and 338/1,032 (32.8%) were under- and over-dosed, respectively. Nineteen (14.5%) patients had a breakthrough-csCMVi, without any associations identified with VCG dosing (p = 0.44). Unlike other cytopenias, a significant association between VGC overdosing and lymphopenia (OR 5.27, 95% CI 1.71-16.22, p = 0.004) was shown. VGC prophylaxis in KTR is frequently inappropriately dosed, albeit without meaningful clinical associations, neither in terms of efficacy nor safety.

Normothermic regional perfusion procurement for abdominal organ donors: techniques and troubleshooting.

Normothermic regional perfusion (NRP) is a novel procurement technique for donation after circulatory death (DCD) in the United States. It was pioneered by cardiothoracic surgery programs and is now being applied to abdominal-only organ donors by abdominal transplant programs. Multiple technical approaches can be used for abdominal-only NRP DCD donors and this review describes these techniques. NRP has been associated with higher utilization of organs, particularly liver and heart grafts, from DCD donors and with better recipient outcomes. There are lower rates of delayed graft function in kidney transplant recipients and lower rates of ischemic cholangiopathy in liver transplant recipients. These benefits are driving increased interest from abdominal transplant programs in using NRP for DCD procurements. This paper describes the technical aspects of NRP DCD that allow for maximization of its use based on different donor and policy characteristics.

Therapeutic Hypothermia in Low-Risk Nonpumped Brain-Dead Kidney Donors

Delayed graft function in kidney-transplant recipients is associated with increased financial cost and patient burden. In donors with high Kidney Donor Profile Index whose kidneys are not pumped, therapeutic hypothermia has been shown to confer a protective benefit against delayed graft function. To determine whether hypothermia is superior to normothermia in preventing delayed graft function in low-risk nonpumped kidney donors after brain death. In a multicenter randomized clinical trial, brain-dead kidney donors deemed to be low risk and not requiring machine perfusion per Organ Procurement Organization protocol were prospectively randomized to hypothermia (34.0-35 °C) or normothermia (36.5-37.5 °C) between August 10, 2017, and May 21, 2020, across 4 Organ Procurement Organizations in the US (Arizona, Upper Midwest, Pacific Northwest, and Texas). The final analysis report is dated June 15, 2022, based on the data set received from the United Network for Organ Sharing on June 2, 2021. A total of 509 donors (normothermia: n = 245 and hypothermia: n = 236; 1017 kidneys) met inclusion criteria over the study period. Donor hypothermia (34.0-35.0 °C) or normothermia (36.5-37.5 °C). The primary outcome was delayed graft function in the kidney recipients, defined as the need for dialysis within the first week following kidney transplant. The primary analysis follows the intent-to-treat principle. A total of 934 kidneys were transplanted from 481 donors, of which 474 were randomized to the normothermia group and 460 to the hypothermia group. Donor characteristics were similar between the groups, with overall mean (SD) donor age 34.2 (11.1) years, and the mean donor creatinine level at enrollment of 1.03 (0.53) mg/dL. There was a predominance of Standard Criteria Donors (98% in each treatment arm) with similar low mean (SD) Kidney Donor Profile Index (normothermia: 28.99 [20.46] vs hypothermia: 28.32 [21.9]). Cold ischemia time was similar in the normothermia and hypothermia groups (15.99 [7.9] vs 15.45 [7.63] hours). Delayed graft function developed in 87 of the recipients (18%) in the normothermia group vs 79 (17%) in the hypothermia group (adjusted odds ratio, 0.92; 95% CI, 0.64-1.33; P = .66). The findings of this study suggest that, in low-risk non-pumped kidneys from brain-dead kidney donors, therapeutic hypothermia compared with normothermia does not appear to prevent delayed graft function in kidney transplant recipients. ClinicalTrials.gov Identifier: NCT02525510.

Effect of Spironolactone on Kidney Function in Kidney Transplant Recipients: A Randomized Placebo-Controlled Clinical Trial.

Long-term kidney allograft survival is hampered by progressive interstitial fibrosis and tubular atrophy. The SPIREN trial tested the hypothesis that the mineralocorticoid receptor antagonist spironolactone stabilizes kidney function and attenuates glomerular barrier injury in kidney transplant patients treated with calcineurin inhibitors. Randomized, placebo-controlled, double blind clinical trial including 188 prevalent kidney transplant patients. Patients were randomized to spironolactone or placebo for three years. Glomerular filtration rate was measured along with proteinuria and kidney fibrosis. The primary endpoint was change in measured glomerular filtration rate. Secondary outcomes were 24h proteinuria, kidney allograft fibrosis and cardiovascular events. Measured glomerular filtration rates, 24h proteinuria and blood pressure were determined yearly. Kidney biopsies were collected at baseline and after two years (n=48). Fibrosis was evaluated by quantitative stereology and classified according to Banff. The groups were comparable at baseline except for slightly older allografts in the spironolactone group. Spironolactone reduced measured glomerular filtration rates (up to -7.6 (95% CI -10.9;-4.3) ml/min compared to placebo) independently of time since transplantation and blood pressure with no impact on the kidney function curve over time and reduced 24h proteinuria after one year. There was no significant effect of spironolactone on the development of interstitial fibrosis. Spironolactone added to standard therapy for three years in kidney transplant patients did not improve kidney function, long-term proteinuria or interstitial fibrosis.

Prevention of Delayed Graft Function in Kidney Transplant Recipients through a Continuous Infusion of the Prostaglandin Analogue Iloprost: A Single-Center Prospective Study.

Delayed graft function (DGF) is common after kidney transplantation from deceased donors and may significantly affect post-transplant outcomes. This study aimed to evaluate whether an innovative approach, based on the administration of the intravenous prostaglandin analogue iloprost, could be beneficial in reducing the incidence of DGF occurring after kidney transplantation from deceased donors. This prospective, randomized (1:1), placebo-controlled study enrolled all consecutive patients who received a kidney transplant from a deceased donor from January 2000 to December 2012 and who were treated in the peri-transplant period with the prostaglandin analogue iloprost at 0.27 μg/min through an elastomeric pump (treatment group) or with a placebo (control group). A total of 476 patients were included: DGF was reported in 172 (36.1%) patients in the entire cohort. The multivariate analysis showed that the donor's age > 70 years (OR 2.50, 95% confidence interval (CI): 1.40-3.05, p < 0.001), cold ischemia time > 24 h (OR 2.60, 95% CI: 1.50-4.51, p < 0.001), the donor's acute kidney injury (OR 2.71, 95% CI: 1.61-4.52, p = 0.021) and, above all, the recipient's arterial hypotension (OR 5.06, 95% CI: 2.52-10.1, p < 0.0001) were the strongest risk factors for developing post-transplant DGF. The incidence of DGF was 21.4% in the treatment group and 50.9% in the control group (p < 0.001). Interestingly, among patients who developed DGF, those who received iloprost had a shorter duration of post-transplant DGF (10.5 ± 8.3 vs. 13.4 ± 6.7, days, p = 0.016). This study showed that the use of a continuous infusion of iloprost could safely and effectively reduce the incidence of DGF in recipients of deceased-donor kidneys, allowing a better graft functionality as well as a better graft survival.

Treatment of BK Polyomavirus-Associated Nephropathy in Paediatric Kidney Transplant Recipients: Leflunomide Versus Cidofovir.

BK polyomavirus-associated nephropathy is a clinicopathological entity that negatively affects graft function in kidney transplant recipients. We compared the efficacy of leflunomide and cidofovir to treat BK polyomavirus-associated nephropathy in pediatric kidney transplant recipients. Medical records of pediatric recipients with BK viremia for the period 2004 through 2019 were reviewed retrospectively, and patients diagnosed with BK polyomavirusassociated nephro-pathy were included in the study. A serum BK virus level above 104 copies/mL was accepted as BK viremia. We defined BK polyomavirusassociated nephropathy as detection of BK virus SV40 antigen on immunochemistry staining of renal graft tissue accompanied by signs of tubulointerstitial nephritis or elevated serum creatinine in addition to BK viremia. Of 304 kidney transplant recipients, 53 had persistent BK viremia; 36 of these patients (61.1% male) were included in the study with the diagnosis of BK polyomavirus-associated nephropathy. Twelve patients (33.3%) received cidofovir, and 14 (38.8%) received leflunomide. Results were similar between the cidofovir and leflunomide groups for serum creatinine level at last follow-up (0.91 ± 0.29 vs 0.94 ± 0.37 mg/dL, respectively; P = .843) and graft failure rate (8.3% vs 14.2%, respectively; P = .632). Graft failure was observed in 8.3% of patients with BK polyomavirus-associated nephropathy. Leflunomide and cidofovir showed similar efficacy for treatment of BK polyomavirus-associated nephropathy.

Role of Serum and Urine Neutrophil Gelatinase-Associated Lipocalin as Biomarkers for Assessing Graft Function in Kidney Transplant Recipients

Role of Serum and Urine Neutrophil Gelatinase-Associated Lipocalin as Biomarkers for Assessing Graft Function in Kidney Transplant Recipients

Effect of Favipiravir on kidney function in kidney transplant recipients with COVID-19 infection: a propensity scores inverse weighting (stabilized) with double adjustment analysis

Effect of Favipiravir on kidney function in kidney transplant recipients with COVID-19 infection: a propensity scores inverse weighting (stabilized) with double adjustment analysis

Difficult-to-Treat Rejections in Kidney Transplant Recipients: Our Experience with Everolimus-Based Quadruple Maintenance Therapy.

All chronic and treatment-resistant acute rejections are "difficult-to-treat" and lead to progressive loss of graft function in kidney transplant recipients (KTR), as no effective treatment exists for such rejections to date. We review our experience with a novel strategy to treat such rejections by adding everolimus as a "rescue" to conventional triple maintenance therapy with prednisolone, mycophenolate mofetil and calcineurin inhibitor. We retrospectively analysed data in 28 KTR who received everolimus-based quadruple therapy at our institution for biopsy-proven chronic active T cell-mediated or antibody-mediated rejection (n = 19) or treatment-resistant acute rejections (n = 9) between 2011-2017. The primary outcome was 5-year death-censored graft survival. Main secondary outcomes were response to treatment defined by stable or improved graft function, 5-year patient survival and discontinuation rate of treatment. The Kaplan-Meier estimate for 5-year death-censored graft survival was 79% in all patients, 90% for patients with chronic active T cell-mediated rejections, 78% for chronic active antibody-mediated rejection and 67% for acute rejections. Response to treatment was achieved in 43% and 5-year patient survival was 94%. Treatment was stopped in 12 (43%) patients due to adverse events. Everolimus-based maintenance quadruple therapy, despite high rate of everolimus discontinuation due to adverse events, may be a valid approach in a subset of kidney transplant recipients with such difficult-to-treat rejections, which otherwise would lead to a high rate of graft loss.

β-Trace Protein and β2-Microglobulin do not Improve Estimation of Glomerular Filtration Rate in Kidney Transplant Recipients Compared With Creatinine and Cystatin C

Reliable estimates of glomerular filtration rate (eGFR) are important for detecting changes in graft function in kidney transplant recipients. Current eGFR equations are based on plasma creatinine and/or cystatin C; however, these are associated with significant bias. This study investigated if equations based on β-trace protein (BTP) and β2-microglobulin (B2M) performed better than the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on creatinine and cystatin C among kidney transplant recipients. We included samples and data from the clinical trial CONTEXT. Glomerular filtration rate (GFR) was measured by plasma clearance of an exogenous marker. The eGFR was calculated using the CKD-EPI equations for estimating GFR from BTP and/or B2M and the 2021 CKD-EPI creatinine and creatinine-cystatin C equations. The GFR estimates were evaluated 3 (n=82) and 12 (n=64) months after transplant using mean bias, precision, and accuracy. Furthermore, we analyzed the ability of the equations to correctly classify the direction of changes in measured GFR from 3 to 12 months. Among the BTP- and B2M-based equations, the combined eGFR-BTP-B2M performed best with respect to precision (SD=7.64 mL/min/1.73 m2) and accuracy (±10% from measured GFR=36%). The eGFR-BTP-B2M and the eGFR-creatinine-cystatin C (2021) performed similarly when comparing precision, accuracy, and residuals (P=.481). The BTP- and/or B2M-based equations did not perform better than the eGFR-creatinine-cystatin C (2021) in correctly classifying the direction of changes in measured GFR from 3 to 12 months. β-trace protein and/or B2M do not improve the estimation of GFR when compared with creatinine- and cystatin C-based 2021 CKD-EPI equations.

Early conversion to belatacept-based immunosuppression regimen promotes improved long-term renal graft function in kidney transplant recipients

BackgroundBelatacept has been demonstrated as an effective alternative immunosuppressant in kidney transplant recipients. This study focuses on outcomes of early and late conversion to Belatacept-based immunosuppression after kidney transplant. Materials and methodsThis retrospective analysis of a prospectively collected database included all adult kidney transplants patients at SUNY Upstate Medical Hospital from 1 January 2014 to 30 December 2022. Early conversion was defined as all conversions done at <6 months after kidney transplantation, and late conversion to belatacept was defined as conversion at >6 months after kidney transplantation. ResultsOut of 61 patients included in this study, 33 patients (54%) were in the early conversion group, and 28 patients (46%) were in the late conversion group. The mean eGFR in the early conversion group was 26.73 ± 16.26 ml/min/1.73 m2 before conversion to belatacept, which improved to 45.3 ± 21.01 ml/min/1.73 m2 at one-year post-conversion (p = 0.0006). Furthermore, eGFR changes in the late conversion group were insignificant, with 46.30 ± 15.65 ml/min/1.73 m2 before conversion to belatacept, and 44.76 ± 22.91 ml/min/1.73 m2 after one year of follow-up (p = 0.72). All four biopsy-proven allograft rejections in the early conversion group were acute T-cell-mediated rejections (ATMR). In the late conversion group, out of three biopsy-proven rejections, one was chronic antibody-mediated rejection (CAMR), one was ATMR, and one was mixed ATMR/CAMR. All four patients with ATMR rejection received mycophenolic acid (MPA) as part of their immunosuppressive regimen, and none received tacrolimus. The one-year post-conversion allograft survival rate in early and late conversion groups was 100%. However, the one-year post-conversion patient survival rate was 90.9% in the early conversion group and 100% in the late conversion group (P = 0.11). ConclusionsEarly post-transplant conversion to belatacept can improve the eGFR more meaningful when compared to late conversion. Patients who receive belatacept and MPA rather than tacrolimus may have increased rates of T-cell-mediated rejection.

Choosing fluids to reduce the risk of delayed graft function after deceased donor kidney transplantation

Delayed graft function (DGF) after deceased donor kidney transplantation, defined clinically as the need for at least one dialysis session within the first week after transplantation, is a common occurrence. 1 Swanson KJ Bhattarai M Parajuli S Delayed graft function: current status and future directions. Curr Opin Organ Transplant. 2023; 28: 1-7 Crossref PubMed Scopus (0) Google Scholar Use of organs that are predisposed to DGF is increasing, 2 NHS Blood and TransplantOrgan and tissue donation and transplantation. Activity Report 2021/22. nhsbtdbe.blob.core.windows.net/umbraco-assets-corp/27108/activity-report-2021-2022.pdfDate accessed: March 23, 2023 Google Scholar meaning it is important to consider the clinical sequelae of DGF. In a systematic review and meta-analysis of 38 studies, 3 Li MT Ramakrishnan A Yu M et al. Effects of delayed graft function on transplant outcomes: a meta-analysis. Transplant Direct. 2023; 9: e1433 Crossref PubMed Scopus (1) Google Scholar DGF was associated with adverse short-term and long-term outcomes, including risk for rejection, graft failure, and (in single-centre studies only) all-cause mortality. Some studies suggest the duration of DGF is more important than its occurrence. 4 Schrezenmeier E Müller M Friedersdorff F et al. Evaluation of severity of delayed graft function in kidney transplant recipients. Nephrol Dial Transplant. 2022; 37: 973-981 Crossref PubMed Scopus (2) Google Scholar However, any DGF has a real-world impact on patients and can influence decision making for clinicians. For example, a third of North American transplant professionals indicated in a survey that the risk of DGF had a role in their willingness to accept organs, 5 Jadlowiec CC Hippen B Gill J et al. Current opinions on DGF management practices: a survey of the United States and Canada. Clin Transplant. 2023; 37: e14949 Crossref PubMed Scopus (0) Google Scholar and strategies to reduce DGF are a clinical priority. A simple intervention to reduce DGF might relate to optimising intravenous fluid replacement. Isotonic sodium chloride (0·9% saline) is the standard of care in many transplantation units. However, 0·9% saline might be harmful due to its high chloride content, which causes metabolic acidosis and can promote acute kidney injury, thus DGF. 6 Yunos NM Bellomo R Hegarty C Story D Ho L Bailey M Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA. 2012; 308: 1566-1572 Crossref PubMed Scopus (844) Google Scholar Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trialAmong patients receiving a deceased donor kidney transplant, intravenous fluid therapy with balanced crystalloid solution reduced the incidence of DGF compared with saline. Balanced crystalloid solution should be the standard-of-care intravenous fluid used in deceased donor kidney transplantation. Full-Text PDF

#5547 SERUM PERIOSTIN IN KIDNEY TRANSPLANT RECIPIENTS AS A NOVEL BIOMARKER PREDICTING RENAL FUNCTION LOSS

Abstract Background and Aims Experimental studies have shown periostin is expressed throughout organogenesis, particularly within the kidney interstitium. Periostin is enhanced in different tissues of patients with nephropathy and has been considered as a candidate biomarker of kidney injury. Method Retrospective analysis of electronic medical record of one hundred and five kidney transplant recipients (KTRs) was performed. Only patients under sequential ambulatory care, with a history of at least 2 years post-transplant were included. Median (IQR) follow-up and time post-transplant was 4.42 (2.65, 4.58) and 4.29 (3.04, 8.07) years, respectively. Additionally, thirty-two health volunteers (HV) were enrolled. Biochemical testing was performed using commercially-available immunoassays. Results Median [IQR] serum periostin was significantly lower in KTRs as compared with HV (959 [732, 1204] vs. 1176 [997, 1408]; P&amp;lt;0.01). Higher serum periostin was observed in male patients (7.01 [6.84, 7.22] vs. 6.79 [6.64, 7.07], P&amp;lt;0.05) and a significant relationship was noted for interleukin 6 (IL6; r=0.24, P=0.01) and baseline estimated glomerular filtration (eGFR) (r=0.20, P=0.04). Patient age (P=0.60), body-mass index P=0.08), cardiovascular disease (P=0.31), diabetes (P=0.45), current smoker status (P=0.27), nor anemia (P=0.23) were not associated with serum periostin. In a generalized additive model adjusted for baseline renal function and IL-6, serum periostin showed a signficant nonlinear association (P=0.04) with eGFR change over follow-up. Conclusion Previous studies reported an association between periostin expression and the severity of histological injury within the kidney in both inflammatory and non-inflammatory conditions. Serum periostin may be a potential marker aiding in prediction of renal function in KTRs.

Calcification Propensity (T50) Predicts a Rapid Decline of Renal Function in Kidney Transplant Recipients.

Serum creatinine level, proteinuria, and interstitial fibrosis are predictive of renal prognosis. Fractional excretion of phosphate (FEP)/FGF23 ratio, tubular reabsorption of phosphate (TRP), serum calcification propensity (T50), and Klotho's serum level are emerging as determinants of poor kidney outcomes in CKD patients. We aimed at analysing the use of FGF23, FEP/FGF23, TRP, T50, and Klotho in predicting the rapid decline of renal function in kidney allograft recipients. We included 103 kidney allograft recipients in a retrospective study with a prospective follow-up of 4 years. We analysed the predictive values of FGF23, FEP/FGF23, TRP, T50, and Klotho for a rapid decline of renal function defined as a drop of eGFR > 30%. During a follow-up of 4 years, 23 patients displayed a rapid decline of renal function. Tertile of FGF23 (p value = 0.17), FEP/FGF23 (p value = 0.78), TRP (p value = 0.62) and Klotho (p value = 0.31) were not associated with an increased risk of rapid decline of renal function in kidney transplant recipients. The lower tertile of T50 was significantly associated with eGFR decline >30% with a hazard ratio of 3.86 (p = 0.048) and remained significant in multivariable analysis. T50 showed a strong association with a rapid decline of renal function in kidney allograft patients. This study underlines its role as an independent biomarker of loss of kidney function. We found no association between other phosphocalcic markers, such as FGF23, FEP/FGF23, TRP and Klotho, with a rapid decline of renal function in kidney allograft recipients.