Kidney Allograft Function Research Articles

Implantable Cardioverter Defibrillators in Prevention of Sudden Cardiac Death in Kidney Transplant Recipients: A Case Series and an Appraisal of Current Evidence.

Background: Cardiovascular diseases, including sudden cardiac death (SCD), are the leading cause of mortality among kidney transplant recipients (KTRs). While implantable cardioverter defibrillators (ICDs) are established for SCD prevention in the general population, data on the benefits in patients with CKD is scarce and controversial, and there is no established general consensus on their use in this group of patients. Furthermore, data for KTRs are lacking. The aim of this study is to present our experience with ICDs in KTRs and evaluate the outcomes in this population. Methods: We retrospectively analyzed medical records of KTRs who received a kidney allograft between October 1973 and December 2023 and received ICDs for the prevention of SCD. Results: Of 2282 KTRs, 10 patients (0.44%) underwent an ICD implantation with an average age of 60.6 years at the time of implantation; 9 were male. Primary prevention of SCD was the most common indication, with only one patient receiving an ICD following sudden cardiac arrest. The female patient received an ICD while on dialysis, and the rest of the patients received ICDs in the posttransplant period with an average time of 9.1 years after KT. Kidney allograft function was reduced in all patients at the time of the ICD implantation with an average estimated glomerular filtration rate (eGFR) of 44 mL/min/1.73 m2. No ICD-related complications were recorded. Six patients are alive with an average follow-up of 5.2 years. Conclusions: ICD implantation in carefully selected KTRs may offer survival benefits and can be a valuable tool in preventing SCD. Larger studies are needed to confirm these findings and establish clear guidelines for ICD use in this specific population.

Deceased donor urinary Dickkopf-3 associates with future allograft function following kidney transplantation

Predicting future kidney allograft function is challenging. Novel biomarkers, such as urinary Dickkopf-3 (uDKK3), may help guide donor selection and improve allograft outcomes. In this prospective multicenter pilot trial, we investigated whether donor uDKK3 reflects organ quality and is associated with future allograft function. We measured uDKK3/crea ratios (uDKK3/crea) from 95 deceased and 46 living kidney donors. Prenephrectomy uDKK3/crea levels were 100× higher in deceased than in living donors (9888 pg/mg vs 113 pg/mg; P < .001). Among deceased donor transplantations, recipients were stratified by their corresponding uDKK3/crea donor levels ranging below (group A, n = 68) or above (group B, n = 65) median. The primary end point of best estimated glomerular filtration rate (eGFR) within the first 3 months after kidney transplantation was superior in group A (56.3 mL/min/1.73 m2) than that in group B (44.2 mL/min/1.73 m2; P = .0139). Second, the composite clinical end point consisting of death, allograft failure or eGFR decline >50% occurred less frequent in group A. By mixed linear regression modeling, donor uDKK3/crea remained an independent predictor of eGFR after transplantation, with a slope of −4.282 mL/min/1.73 m2 per logarithmic increase in donor uDKK3/crea. In summary, uDKK3 may serve as a noninvasive, donor-dependent biomarker for assessing organ quality and future allograft function.

Abstract P363: Prevelance of Hypertension in Kidney Transplant Recepients as Determined by Ambulatory BP Monitoring (ABPM)

Background: Cardiovascular disease remains the most common cause of death among kidney transplant recipients, with hypertension being one of the most prevalent risk factors. Understanding the current prevalence of hypertension in this population is critical to help shape post-transplant care policies and guidelines and ensure proper management of CVD risk. Methods: We included all kidney transplant recipients who received their transplant between 2019 and 2023 at our center and who completed 24-hour ABPM at 12 months post-transplant. We reported data in mean (SD) unless noted otherwise. BP was categorized per AHA guidelines. This study was deemed exempt by the IRB. Results: A total of 940 patients were included in this study. Detailed results are seen in Figure 1 and Table 1. Notable to mention that 60% of the patients had blood pressure &gt; 130/80 mmHg at 12 months post kidney transplant, with the majority being stage 1. Patients with more severe hypertension tended to be older, had lower eGFR, and had more comorbidities. They also had lower diastolic blood pressure than stage 1 HTN patients, consistent with older age. Night-time BP was significantly higher among stage 2 HTN patients. Conclusion: Hypertension remains a prevalent condition post-kidney transplant despite the majority of patients having satisfactory kidney allograft function. Ongoing BP monitoring and assessment of out-of-office BP post-kidney transplantation is critical to ensure control of this important cardiovascular risk factor. 24-hour ABPM has several advantages in this group, including accurate measurement of out-of-office BP and detection of nocturnal hypertension, an independent risk factor for cardiovascular events. Additional studies are needed to describe the hypertension subphenotypes (e.g., sustained vs. masked) and to identify predictors of severe uncontrolled hypertension in this patient population.

Protocol biopsy of kidney allograft enables early detection of BK virus nephropathy to preserve kidney allograft function.

The Banff Working Group has updated the histological classification of BK virus nephropathy (BKVN), highlighting the importance of early detection. However, an early detection strategy for BKVN using biopsy has not yet been established. Our investigation aimed to assess the efficacy of protocol biopsy for the diagnosis of BKVN. We performed a retrospective cohort study of 314 patients who had undergone kidney transplantation between 2006 and 2021. Kidney allograft biopsies were performed as part of a protocol biopsy at 3 months and 1 year post-transplantation. Following the diagnosis of BKVN, the immunosuppressant dose was reduced. Twelve patients (3.8%) were diagnosed with BKVN by biopsy. Most diagnoses are established during the early stages of BKVN (polyomavirus nephropathy class 1 in six, class 2 in five, and class 3 in one). Following the reduction in immunosuppressant dose, kidney allograft function did not deteriorate in any patients. Additionally, test for BK virus DNA in the blood was negative. All but one patient demonstrated histological resolution of BKVN, and the other had a very slight positivity for the simian virus 40 large T antigen. The median follow-up time after BKVN diagnosis was 6 years. One patient developed de novo donor-specific antibody and subclinical acute antibody-mediated rejection that was successfully cured. Our analysis indicates that protocol biopsy may enable the early detection of BKVN, resulting in the preservation of kidney function.

Doppler Ultrasonographic Indexes and Its Relation to Transplanted Kidney (Allograft) Function in Sulaimani City Centre

Doppler Ultrasonographic Indexes and Its Relation to Transplanted Kidney (Allograft) Function in Sulaimani City Centre

Exploring Acute Pancreatitis in Kidney Transplant Recipients: A Multicentre Retrospective Cohort Analysis of Incidence, Causes, and Clinical Outcomes.

Background: The aim of this multicentre retrospective study is to determine the incidence, etiology, clinical characteristics, and outcomes of kidney transplant recipients diagnosed and treated for acute pancreatitis. Methods: We analyzed data from kidney transplant recipients who received kidney allografts between October 1973 and December 2023 and were diagnosed and treated for acute pancreatitis. Results: Of 2482 patients who received kidney allografts, 10 (0.4%) (5 male) were diagnosed with acute pancreatitis, with a mean age of 48.6 years. Patients were diagnosed with acute pancreatitis between 3 weeks and 24 years after the transplantation. Possible etiologies included cholecystolithiasis, COVID-19, hypercalcemia, postprocedural, use of cannabis, trimetoprim-sulphometoxasole, statins, sirolimus, tacrolimus and obesity. There was no suspected etiology in two patients. Patients were treated with aggressive hydration, pain alleviation and antibiotics if indicated. Four patients developed complications. Local complications included peripancreatic collections, pseudocyst, and abscesses formation, while systemic complications occurred in the form of Cytomegalovirus (CMV) reactivation and urinary tract infection. All patients survived with preserved kidney allograft function. Conclusions: Acute pancreatitis in kidney transplant recipients is rare. However, it may be linked to significant morbidity and mortality. While symptoms may be nonspecific and brought on by a variety of viral and non-infectious illnesses, as well as adverse effects from immunosuppressive medications, a high degree of awareness is required.

Taurine Deficiency Is a Hallmark of Injured Kidney Allografts.

Taurine is one of the most abundant amino acids in humans. Low taurine levels are associated with cellular senescence, mitochondrial dysfunction, DNA damage, and inflammation in mouse, all of which can be reversed by supplementation. It is unknown whether taurine metabolism is associated with kidney allograft function and survival. We performed urine metabolomic profiling of kidney transplant recipients in the early and late phases after transplantation combined with transcriptomic analysis of human kidney allografts. Single-nucleus RNA sequencing data sets of mouse kidneys after ischemia-reperfusion injury were analyzed. We analyzed the association of urinary taurine levels and taurine metabolism genes with kidney function, histology, and graft survival. Urine taurine concentrations were significantly lower in kidney transplant recipients who experienced delayed graft function. In a mouse model of ischemia-reperfusion injury, the taurine biosynthesis gene, CSAD , but not the taurine transporter SLC6A6 , was repressed. In the late stage of transplantation, low level of taurine in urine was associated with impaired kidney function and chronic structural changes. Urine taurine level in the lowest tertile was predictive of graft loss. Expression of the taurine transporter SLC6A6 in the upper median, but not CSAD , was associated with chronic kidney injury and was predictive of graft loss. Low urine taurine level is a marker of injury in the kidney allograft, is associated with poor kidney function, is associated with chronic histological changes, and is predictive of graft survival. The differential expression of CSAD and SLC6A6 , depending on the time after transplantation and marks of injury, highlights different mechanisms affecting taurine metabolism.

Acute pancreatitis as a complication of acute COVID-19 in kidney transplant recipients.

Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019 (COVID-19) but its full correlation with COVID-19 infection remains unknown. To identify acute pancreatitis' occurrence, clinical presentation and outcomes in a cohort of kidney transplant recipients with acute COVID-19. A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute COVID-19. Data were obtained from hospital electronic medical records. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal swab. Four hundred and eight out of 1432 (28.49%) patients who received a renal allograft developed COVID-19 disease. The analyzed cohort included 321 patients (57% males). One hundred and fifty patients (46.7%) received at least one dose of the anti-SARS-CoV-2 vaccine before the infection. One hundred twenty-five (39.1%) patients required hospitalization, 141 (44.1%) developed pneumonia and four patients (1.3%) required mechanical ventilation. Treatment included immunosuppression modification in 233 patients (77.1%) and remdesivir in 53 patients (16.6%), besides the other supportive measures. In the study cohort, only one transplant recipient (0.3%) developed acute pancreatitis during acute COVID-19, presenting with abdominal pain and significantly elevated pancreatic enzymes. She survived without complications with a stable kidney allograft function. Although rare, acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant recipients. The mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.

Intravoxel incoherent motion diffusion-weighted imaging for predicting kidney allograft function decline: comparison with clinical parameters

ObjectiveTo evaluate the added benefit of diffusion-weighted imaging (DWI) over clinical parameters in predicting kidney allograft function decline.MethodsData from 97 patients with DWI of the kidney allograft were retrospectively analyzed. The DWI signals were analyzed with both the mono-exponential and bi-exponential models, yielding total apparent diffusion coefficient (ADCT), true diffusion (D), pseudo-diffusion (D*), and perfusion fraction (fp). Three predictive models were constructed: Model 1 with clinical parameters, Model 2 with DWI parameters, and Model 3 with both clinical and DWI parameters. The predictive capability of each model was compared by calculating the area under the receiver-operating characteristic curve (AUROC).ResultsForty-five patients experienced kidney allograft function decline during a median follow-up of 98 months. The AUROC for Model 1 gradually decreased with follow-up time > 40 months, whereas Model 2 and Model 3 maintained relatively stable AUROCs. The AUROCs of Model 1 and Model 2 were not statistically significant. Multivariable analysis showed that the Model 3 included cortical D (HR = 3.93, p = 0.001) and cortical fp (HR = 2.85, p = 0.006), in addition to baseline estimated glomerular filtration rate (eGFR) and proteinuria. The AUROCs for Model 3 were significantly higher than those for Model 1 at 60-month (0.91 vs 0.86, p = 0.02) and 84-month (0.90 vs 0.83, p = 0.007) follow-up.ConclusionsDWI parameters were comparable to clinical parameters in predicting kidney allograft function decline. Integrating cortical D and fp into the clinical model with baseline eGFR and proteinuria may add prognostic value for long-term allograft function decline.Critical relevance statementOur findings suggested that cortical D and fp derived from IVIM-DWI increased the performance to predict long-term kidney allograft function decline. This preliminary study provided basis for the utility of multi-b DWI for managing patients with a kidney transplant.Key points• Both clinical and multi-b DWI parameters could predict kidney allograft function decline.• The ability to predict kidney allograft function decline was similar between DWI and clinical parameters.• Cortical D and fp derived from IVIM-DWI increased the performance to predict long-term kidney allograft function decline.Graphical

Should Transplant Nephrology Pursue Recognition from the Accreditation Council for Graduate Medical Education (ACGME)?

Kidney transplant is not only the best treatment for patients with advanced kidney disease but it also reduces health care expenditure. The management of transplant patients is complex as they require special care by transplant nephrologists who have expertise in assessing transplant candidates, understand immunology and organ rejection, have familiarity with perioperative complications, and have the ability to manage the long-term effects of chronic immunosuppression. This skill set at the intersection of multiple disciplines necessitates additional training in Transplant Nephrology. Currently, there are more than 250,000 patients with a functioning kidney allograft and over 100,000 waitlisted patients awaiting kidney transplant, with a burgeoning number added to the kidney transplant wait list every year. In 2022, more than 40,000 patients were added to the kidney wait list and more than 25,000 received a kidney transplant. The Advancing American Kidney Health Initiative, passed in 2019, is aiming to double the number of kidney transplants by 2030 creating a need for additional transplant nephrologists to help care for them. Over the past decade, there has been a decline in the Nephrology-as well Transplant Nephrology-workforce due to a multitude of reasons. The American Society of Transplantation Kidney Pancreas Community of Practice created a workgroup to discuss the Transplant Nephrology workforce shortage. In this article, we discuss the scope of the problem and how the Accreditation Council for Graduate Medical Education recognition of Transplant Nephrology Fellowship could at least partly mitigate the Transplant Nephrology work force crisis.

Polygenic risk score for acute rejection based on donor-recipient non-HLA genotype mismatch.

Acute rejection (AR) after kidney transplantation is an important allograft complication. To reduce the risk of post-transplant AR, determination of kidney transplant donor-recipient mismatching focuses on blood type and human leukocyte antigens (HLA), while it remains unclear whether non-HLA genetic mismatching is related to post-transplant complications. We carried out a genome-wide scan (HLA and non-HLA regions) on AR with a large kidney transplant cohort of 784 living donor-recipient pairs of European ancestry. An AR polygenic risk score (PRS) was constructed with the non-HLA single nucleotide polymorphisms (SNPs) filtered by independence (r2 < 0.2) and P-value (< 1×10-3) criteria. The PRS was validated in an independent cohort of 352 living donor-recipient pairs. By the genome-wide scan, we identified one significant SNP rs6749137 with HR = 2.49 and P-value = 2.15×10-8. 1,307 non-HLA PRS SNPs passed the clumping plus thresholding and the PRS exhibited significant association with the AR in the validation cohort (HR = 1.54, 95% CI = (1.07, 2.22), p = 0.019). Further pathway analysis attributed the PRS genes into 13 categories, and the over-representation test identified 42 significant biological processes, the most significant of which is the cell morphogenesis (GO:0000902), with 4.08 fold of the percentage from homo species reference and FDR-adjusted P-value = 8.6×10-4. Our results show the importance of donor-recipient mismatching in non-HLA regions. Additional work will be needed to understand the role of SNPs included in the PRS and to further improve donor-recipient genetic matching algorithms. Trial registry: Deterioration of Kidney Allograft Function Genomics (NCT00270712) and Genomics of Kidney Transplantation (NCT01714440) are registered on ClinicalTrials.gov.

Our Experience of Laparoscopic Living Donor Nephrectomy

Background Donor nephrectomy for living donor kidney transplantation using minimally invasive techniques is a safe procedure that has been used for more than 20 years with excellent results. The total minimally invasive approach offers decreased postoperative pain, better cosmesis, a lower chance of incisional hernia, and a faster recovery time. Methods We present the results of a series of 120 laparoscopic donor nephrectomies performed at our center. The procedures were performed with transperitoneal access using the standard five ports. The main renal artery and vein were ligated using a hemo-o-lock clip. The specimen was extracted through the additional inguinal incision. Results All procedures were performed laparoscopically without conversion to open surgery. The average warm ischemia time was 4.0 min. In all recipients, immediate kidney allograft function was seen. Conclusion Total laparoscopic living donor nephrectomy is a safe procedure that gives the highest benefit to the donor. It was performed successfully in all cases, with a short operative time and no morbidity or mortality.

Improved outcomes of kidney after liver transplantation after the implementation of the safety net policy.

The number of kidney after liver transplants (KALT) increased after the implementation of the United Network of Organ Sharing (UNOS) safety net policy, but the effects of the policy on KALT outcomes remain unknown. Using the UNOS database, we identified KALT between 60 and 365 days from liver transplant from January 1, 2010, to December 31, 2020. The main outcome was 1- and 3-year patient, liver, and kidney graft survival. Secondary outcomes included 6-month and 1-year acute rejection (AR) of liver and kidney, and 1-year kidney allograft function. Of the 256 KALT, 90 were pre-policy and 166 post-policy. Compared to pre-policy, post-policy 1- and 3-year liver graft survival was higher (54% and 54% vs. 86% and 81%, respectively, p <0.001), while 1- and 3-year kidney graft survival (99% and 75% vs. 92% and 79%, respectively, p =0.19), and 1- and 3-year patient survival (99% and 99% vs. 95% and 89%, respectively, p =0.11) were not significantly different. Subgroup analysis revealed similar trends in patients with and without renal failure at liver transplant. Liver AR at 6 months was lower post-policy (6.3% vs. 18.3%, p =0.006) but was similar (10.5% vs. 13%, p =0.63) at 1 year. Kidney AR was unchanged post-policy at 6 months and 1 year. Creatinine at 1 year did not differ post-policy versus pre-policy (1.4 vs. 1.3mg/dL, p =0.07) despite a higher proportion of deceased donors, higher Kidney Donor Profile Index, and longer kidney cold ischemia time post-policy ( p <0.05 for all). This 3-year follow-up after the 2017 UNOS policy revision demonstrated that the safety net implementation has resulted in improved liver outcomes for patients who underwent KALT with no increased AR of the liver or the kidney allografts.

Comparative analysis of Basiliximab and Alemtuzumab induction therapies in blood type A2-to-B kidney transplantation: Impact on kidney function and de novo donor-specific HLA antibodies

PurposeBlood group B kidney transplant candidates have lower transplantation rates and longer waiting times compared to other blood groups. Kidney transplantation from blood group A2-to-B has offered a solution for these patients. This study aimed to investigate the impact of Basiliximab and Alemtuzumab induction therapies on kidney function and de novo donor-specific antibodies (DSA) in blood type A2-to-B kidney transplant recipients within the first 12 months of post-transplant. MethodsA retrospective analysis was conducted on 110 consecutive A2-to-B kidney transplant recipients between January 2015 and December 2022. Of these, 46 (41.8%) received Basiliximab, while 64 (58.2%) received Alemtuzumab as induction therapy. Demographics and comorbidities data were collected and compared between the two groups. Serum samples collected at 4- and 12-month intervals post-transplant were used to assess the presence of de novo DSA. Kidney allograft function was evaluated by monitoring serum creatinine levels and assessing Creatinine Clearance based on 24-h urine collection at various time points. ResultsDuring the follow-up period, 20.00% of patients who received Alemtuzumab developed de novo DSA, whereas none of the patients induced with Basiliximab developed de novo DSA (p = 0.038). Recipients who received Basiliximab were older (mean age = 72.00) and received higher Kidney Donor Profile Index (KDPI) kidneys (mean = 75) compared to those induced with Alemtuzumab (mean age = 58.00, mean KDPI = 49) (p < 0.001), with no significant difference observed in the last follow-up creatinine clearance or creatinine levels between the two groups (p = 0.28). ConclusionThe use of Basiliximab as induction immunosuppression in A2-to-B kidney transplant recipients is associated with a lower incidence of de novo HLA DSA formation without significant differences in overall renal function compared to Alemtuzumab.

Current management of symptomatic vesicoureteral reflux in pediatric kidney transplantation-A European survey among surgical transplant professionals.

Vesicoureteral reflux (VUR) is common in children and adolescents undergoing kidney transplantation (KTx) and may adversely affect allograft kidney function. To explore the current management of symptomatic native and allograft VUR in pediatric KTx recipients, an online survey was distributed to European surgical transplant professionals. Surgeons from 40 pediatric KTx centers in 18 countries participated in this survey. Symptomatic native kidney VUR was treated before or during KTx by 68% of the centers (all/selected patients: 33%/67%; before/during KTx: 89%/11%), with a preference for endoscopic treatment (59%). At KTx, 90% favored an anti-reflux ureteral reimplantation procedure (extravesical/transvesical approach: 92%/8%; preferred extravesical technique: Lich-Gregoir [85%]). Management strategies for symptomatic allograft VUR included surgical repair (90%), continuous antibiotic prophylaxis (51%), bladder training (49%), or noninterventional surveillance (21%). Redo ureteral implantation and endoscopic intervention for allograft VUR were equally reported (51%/49%). This survey shows uniformity in some surgical aspects of the pediatric KTx procedure. However, with regard to VUR, there is a significant variation in practice patterns that need to be addressed by future well-designed and prospective studies. In this way, more robust data could be translated into consensus guidelines for a more standardized and evidence-based management of this common condition in pediatric KTx.

Expression of KIM-1, VEGF and bFGF in the transplanted kidney as predictive factors of kidney allograft function

Expression of KIM-1, VEGF and bFGF in the transplanted kidney as predictive factors of kidney allograft function

Improved Early Post-Transplant Outcomes and Organ Use in Kidney Transplant Using Normothermic Regional Perfusion for Donation after Circulatory Death: National Experience in the US.

Normothermic regional perfusion (NRP) is a technique that is intended to enhance organ transplant outcomes from donation circulatory death (DCD) donors. A retrospective analysis of data from the Scientific Registry of Transplant Recipients was performed. DCD donors were screened for inclusion based on date of donation 2020 or later, and whether the heart was also recovered for transplantation. We grouped donors as either donation after brain death or DCD. DCD donors were further divided into groups including those in which the heart was not recovered for transplant (Non-Heart DCD) and those in which it was, based on recovery technique (thoracoabdominal-NRP [TA-NRP] Heart DCD and Super Rapid Recovery Heart DCD). A total of 219 kidney transplant recipients receiving organs from TA-NRP Heart DCD donors were compared to 436 SRR Super Rapid Recovery DCD, 10,630 Super Rapid Recovery non-heart DCD, and 27,820 donations after brain death recipients. Kidney transplant recipients of TA-NRP DCD allografts experienced shorter length of stay, lower rates of delayed graft function, and lower serum creatinine at the time of discharge when compared with recipients of other DCD allografts. Our analysis demonstrates superior early kidney allograft function when TA-NRP is used for DCD organ recovery.

Robot Yardımlı Böbrek Naklinde Bifazlı Sıvı Tedavisi’nin Etkinliği

Objective: Perioperative fluid treatment is among the factors affecting transplant kidney function. In this study, the efficacy of biphasic fluid treatment on per-operative patient stabilization and allograft kidney functions were evaluated. Material and Methods: Data of 65 robotic living releated donor kidney transplantation performed between 2015-2017 were retrospectively analyzed (16/04/2018, Protocol no 2018-07-13). The patients were divided as preemptive (Group Preemptif: GP, n=27) and non-preemptive group (Group Non-Preemptif: GNP, n=38). Biphasic fluid treatment was used in all cases (Phase 1 = before-vascular anastomosis 1-3 ml/kg/h and phase 2 = after-vascular anastomosis 10-12 ml/kg/h, respectively). Hemodynamic and biochemical status of the patients, early and late allograft kidney function were evaluated. Datas were statistically compared within and between the groups. Results: Hemodynamic/metabolic stability and diuresis were achieved after vascular anastomosis in all patients. There was no difference in the total amount of iv fluid given between the groups, except that the amount of fluid given in phase 1 was significantly less in GP (p&amp;lt;0.05). Pre-operative blood pH and HCO3 values were lower, Na+ and Cl- values were higher in GP(p&amp;lt;0.05). No difference was found in K+ and Ca+2 values at all times and pH values after extubation in both groups. Pre-operative blood urea and creatinine levels were significantly higher in GP (p&amp;lt;0.05) but all decreased to normal on postoperative 1 and 7 days. In long-term follow-up, both groups had similar mortality and rejection rates. Conclusion: Our results support that biphasic fluid treatment is effective to achieve hemodynamic/ metabolic stability and allograft kidney functions in robotic living releated kidney transplantation patients.

The anti-CD40L monoclonal antibody AT-1501 promotes islet and kidney allograft survival and function in nonhuman primates.

Prior studies of anti-CD40 ligand (CD40L)-based immunosuppression demonstrated effective prevention of islet and kidney allograft rejection in nonhuman primate models; however, clinical development was halted because of thromboembolic complications. An anti-CD40L-specific monoclonal antibody, AT-1501 (Tegoprubart), was engineered to minimize risk of thromboembolic complications by reducing binding to Fcγ receptors expressed on platelets while preserving binding to CD40L. AT-1501 was tested in both a cynomolgus macaque model of intrahepatic isletallotransplantation and a rhesus macaque model of kidney allotransplantation. AT-1501 monotherapy led to long-term graft survival in both islet and kidney transplant models, confirming its immunosuppressive potential. Furthermore, AT-1501-based regimens after islet transplant resulted in higher C-peptide, greater appetite leading to weight gain, and reduced occurrence of cytomegalovirus reactivation compared with conventional immunosuppression. These data support AT-1501 as a safe and effective agent to promote both islet and kidney allograft survival and function in nonhuman primate models, warranting further testing in clinical trials.

Longitudinal estimated glomerular filtration rate (eGFR) modeling in long-term renal function to inform clinical trial design in kidney transplantation.

Kidney transplantation is the preferred treatment for individuals with end-stage kidney disease. From a modeling perspective, our understanding of kidney function trajectories after transplantation remains limited. Current modeling of kidney function post-transplantation is focused on linear slopes or percent decline and often excludes the highly variable early timepoints post-transplantation, where kidney function recovers and then stabilizes. Using estimated glomerular filtration rate (eGFR), a well-known biomarker of kidney function, from an aggregated dataset of 4904 kidney transplant patients including both observational studies and clinical trials, we developed a longitudinal model of kidney function trajectories from time of transplant to 6 years post-transplant. Our model is a nonlinear, mixed-effects model built in NONMEM that captured both the recovery phase after kidney transplantation, where the graft recovers function, and the long-term phase of stabilization and slow decline. Model fit was assessed using diagnostic plots and individual fits. Model performance, assessed via visual predictive checks, suggests accurate model predictions of eGFR at the median and lower 95% quantiles of eGFR, ranges which are of critical clinical importance for assessing loss of kidney function. Various clinically relevant covariates were also explored and found to improve the model. For example, transplant recipients of deceased donors recover function more slowly after transplantation and calcineurin inhibitor use promotes faster long-term decay. Our work provides a generalizable, nonlinear model of kidney allograft function that will be useful for estimating eGFR up to 6 years post-transplant in various clinically relevant populations.