Preformed donor-specific HLA antibodies (DSA) are a well-known risk factor in kidney transplantation. There is still considerable debate, however, about the optimal risk stratification among patients with preformed DSA. Additionally, data on the prognostic value of different crossmatch assays in DSA-positive patients are scarce. DSA-positive living kidney transplant recipients were selected from a multicenter study examining 4233 consecutive renal transplants. An additional 7 patients from 2 further centers were included. Flow cytometric crossmatches (FXM), Luminex-based crossmatches, and virtual crossmatches based on C1q- and C3d-binding antibodies (C1qXM and C3dXM) were performed retrospectively using pretransplant sera and lymphocytes isolated from fresh samples. These samples were obtained from 44 donor and recipient pairs from 12 centers. Clinical outcome data and the control group without DSA were compiled from the previous study and were supplemented by data on 10-y death-censored graft survival (10yGS). Between 19% (C3dXM) and 46% (FXM) of crossmatches were positive. Crossmatch-positive patients showed high incidences of antibody-mediated rejection (AMR) within 6 mo (up to 60% in B-cell FXM+ patients). The incidence of AMR in crossmatch-negative patients ranged between 5% (FXM-) and 13% (C1qXM-). 10yGS was significantly impaired in patients with positive T-cell FXM and total FXM compared with both patients without DSA and those with DSA with negative FXM. Especially FXM are useful for risk stratification, as the outcome of DSA-positive, FXM-negative patients is similar to that of DSA-negative patients, whereas FXM-positive patients have both more AMR and decreased 10yGS. Because of their lower sensitivity, the significance of Luminex-based crossmatches, C1qXM, and C3dXM would have to be examined in patients with stronger DSA.

On September 28, 2021, the TransMedics Organ Care System (OCS) became the first normothermic perfusion pump to receive Food and Drug Administration approval in liver transplantation (LT). Since then, perfusion pump use has spread widely because it significantly extends ex vivo organ viability time compared with traditional static cold storage.1 We present a case series of 4 patients who rapidly developed biopsy-proven nodular regenerative hyperplasia (NRH) and portal hypertension after LT with perfusion pump utilization at a single institution in 2022–2024. Pretransplant biopsies for all cases are presented in the case figures. TransMedics OCS mean pump parameters for all cases are included in Table 1. TABLE 1. - Mean TransMedics OCS pump parameters Patient case PF, L/min Hepatic artery flow, L/min Portal vein flow, L/min Mean hepatic artery pressure, mm Hg Systolic hepatic artery pressure mean, mm Hg Diastolic hepatic artery pressure mean, mm Hg Mean portal vein pressure, mm Hg Perfusate temperature, C Perfusate venous saturation, % Perfusate hematocrit, % SDS bile salt, mL/h Arterial lactate initial OCS Arterial lactate final OCS Bile 1 1.98 0.48 1.5 50 74 28 7 33.8 98 27 4 5.31 0.89 15 2 1.87 0.5 1.37 44 70 23 3 33.8 96 36 3 9.69 0.3 75 3 1.88 0.58 1.3 48 77 24 3 33.7 96 23 3 5.15 0.86 30 4 1.75 0.34 1.41 53 72 35 7 33.7 97 32 3 6.65 2.53 25 OCS, Organ Care System; PF, pump flow (total flow of combined portal vein + hepatic artery); SDS, substrate delivery system. CASE 1 Patient 1 is a 56-y-old man with a history of alcohol-associated liver disease and normal baseline renal function whose deceased brain donor (DBD) was a 65-y-old woman with a body mass index (BMI) of 26.8 kg/m2 and a history of chronic hepatitis C (nucleic acid test–) who died after a cerebrovascular accidence. The donor organ was placed on the TransMedics OCS for 7 h and 38 min. The patient experienced a brief episode of hypotension intraoperatively during this successful whole liver, duct-to-duct transplantation. Relevant laboratory tests on postoperative day (POD) 1 included aspartate aminotransferase (AST) 143 U/L, alanine transaminase (ALT) 80 U/L, alkaline phosphatase (ALP) 46 IU/L, total bilirubin (tbili) 4.7 mg/dL, blood urea nitrogen (BUN) 41 mg/dL, creatinine (Cr) 1.7 mg/dL, platelets 107/L, and international normalized ratio (INR) 2.2. He was started on tacrolimus, mycophenolate, and prednisone post-LT and remained admitted after his transplantation because of uptrending bilirubin and ALP. On POD 9, the patient developed an acute kidney injury (AKI) with Cr 2.2 mg/dL and BUN 43 mg/dL. Post-LT duplex ultrasound demonstrated normal hepatic vasculature flow. The patient progressively developed clinically significant portal hypertension (CSPH), with ascites and hepatic hydrothorax. Transjugular biopsy (TJB) 4 wk post-LT showed a portosystemic gradient of 18 mm Hg, a right atrium (RA) pressure of 12 mm Hg, and a free hepatic vein pressure (HVP) of 16 mm Hg; pathology did not show signs of rejection but did show NRH (Figure 1). The patient had an extensive workup for secondary causes of CSPH, including a normal cardiac workup, normal inferior vena cava (IVC) venogram, and no evidence of splenic steal on angiogram. A splenic artery embolization was performed, given prior data that suggest this may improve post-LT portal pressure gradients.2 The patient became progressively oliguric, requiring escalating diuretic doses and treatment for hepatorenal syndrome. Renal replacement therapy (RRT) was initiated at 7 wk post-LT for volume management, leading to clinical improvement. RRT was stopped by 13 wk post-LT with resolution of portal hypertension symptoms without continued need for diuretics. Over the next year, his course was complicated by anastomotic biliary strictures requiring multiple endoscopic retrograde cholangiopancreatography with stent placements without recurrence of portal hypertension symptoms. Twelve months post–initial LT, the patient underwent repeat LT. Explant pathology of the allograft liver showed NRH.FIGURE 1.: Pre/posttransplant biopsies for case 1. Pre- and posttransplant biopsies for case 1. A, Biopsy of pretransplant donor liver without significant pathology findings (reticulin, ×100). B, Biopsy of pretransplant donor in H&E stain (×100) without significant pathology findings. C, Biopsy of posttransplant liver showing alternately expanded and compressed hepatic plates, suggestive of NRH (reticulin, ×100). D, Biopsy of posttransplant liver in H&E stain (×100) showing evidence of NRH. H&E, hematoxylin and eosin; NRH, nodular regenerative hyperplasia.CASE 2 Patient 2 is a 50-y-old man with a history of metabolic dysfunction-associated steatotic liver disease with normal baseline renal function whose DBD was a 59-y-old man with a BMI of 43.4 who died from cardiac arrest. The donor organ was placed on the TransMedics OCS for 18 h and 29 min. There were no intraoperative episodes of hypotension in this successful duct-to-duct LT with a standard caval replacement technique. POD 1 laboratory tests showed BUN 24 mg/dL, Cr 1.1 mg/dL, AST 753 U/L, ALT 598 U/L, tbili 1.5 mg/dL, platelets 55/L, and INR 1.7. The patient was started on tacrolimus, mycophenolate, and prednisone and discharged on POD 10. Within 3 wk of transplantation, the patient developed worsening ascites and lower extremity edema. He was readmitted for volume overload and found to have an AKI with BUN 73 mg/dL and Cr 1.9 mg/dL. Liver duplex ultrasound showed normal portal vein and hepatic artery flow. TJB at 4 wk post-LT revealed a portosystemic gradient of 11 mm Hg, with a free HVP of 18 mm Hg and RA pressure of 25 mm Hg; the tissue sample was small limiting analysis. Right heart catheterization showed elevated filling pressures (RA 14 mm Hg) and preserved cardiac index. He was trialed on diuretics as well as dopamine but did not clinically respond. The hepatic venogram did not show IVC narrowing. Repeat TJB 6 wk post-LT showed an increased portosystemic gradient to 14 mm Hg, with pathology notable for NRH (Figure 2). Patient 2 underwent an extensive workup for secondary causes of portal hypertension, notable for possible preferential flow toward the splenic artery, leading this patient to undergo a splenic artery embolization. He started RRT 7 wk post-LT for aggressive volume management with clinical improvement and stopped RRT within 10 wk post-LT. His maintenance diuretic therapy was weaned and eventually stopped. Repeat TJB at 11 wk post-LT demonstrated a portosystemic pressure gradient of 13 mm Hg with a free HVP of 5 mm Hg. Pathology remained suggestive of NRH.FIGURE 2.: Pre/Posttransplant biopsies for case 2. Pre- and posttransplant biopsies for case 2. A, Biopsy of pretransplant donor liver without significant pathology findings (reticulin, ×40). B, Biopsy of pretransplant donor in H&E stain (×40) without significant pathology findings. C, Posttransplant liver biopsy highlighting the key feature of NRH with alternately expanded (white arrows) and compressed (black arrow) hepatic plates (Reticulin, ×100). D, Biopsy of posttransplant liver in H&E stain (×100) showing evidence of NRH. H&E, hematoxylin and eosin; NRH, nodular regenerative hyperplasia.CASE 3 Patient 3 is a 53-y-old woman with a history of metabolic dysfunction-associated steatotic liver disease and normal baseline renal function whose DBD was a 57-y-old man with a BMI of 28.5 and a history of alcohol use. The donor organ was placed on the TransMedics OCS for 12 h and 13 min. The patient underwent successful duct-to-duct LT with the standard caval replacement technique. Intraoperatively, there were no prolonged episodes of hypotension. POD 1 laboratory tests were notable for BUN 26 mg/dL, Cr 1.0 mg/dL, AST 1970 U/L, ALT 650 U/L, tbili 2.9 mg/dL, platelets 60/L, and INR 1.8. The patient was started on tacrolimus, mycophenolate, and prednisone post-LT and discharged on POD 6. The patient was seen in the clinic on POD 10 where she had increasing ascites and lower extremity edema and was readmitted for diuretics and paracentesis. Doppler ultrasound showed main hepatic artery stenosis at the anastomosis site, and TJB and venogram showed narrowing at the IVC superior anastomosis with a 9-mm Hg gradient across and an 18-mm Hg portal/RA pressure gradient. Pathology showed moderate T cell–mediated allograft rejection, which was treated. At 6 wk post-LT, she underwent IVC angioplasty with a reduction of the gradient across the anastomosis to 3 mm Hg. Repeat TJB showed a 16-mm Hg portosystemic gradient, and pathology showed treated acute cellular rejection with NRH (Figure 3). Because of persistent AKI and concern for hepatorenal physiology, the patient was started on RRT. She had a prolonged admission and was discharged at 10 wk post-LT with RRT stopped 12 wk post-LT with continuation of maintenance diuretics.FIGURE 3.: Pre/posttransplant biopsies for case 3. Pre- and posttransplant biopsies for case 3. A, Biopsy of pretransplant donor liver without significant pathology findings (H&E, ×100). No reticulin stains were performed. B, Biopsy of posttransplant liver in H&E stain (×100) showing evidence of NRH. C, Reticulin stain of posttransplant liver biopsy shows alternately expanded and compressed hepatic plates, suggestive of NRH (reticulin, ×100). H&E, hematoxylin and eosin; NRH, nodular regenerative hyperplasia.CASE 4 Patient 4 is a 4-y-old male child with end-stage liver disease because of progressive familial intrahepatic cholestasis and normal renal function whose DBD was a previously healthy 11-y-old girl child. The donor organ was placed on the TransMedics OCS for 4 h and 55 min. The patient was transplanted with the left lateral segment of the donor organ in a piggyback manner with no intraoperative hypotension. POD 1 laboratory tests showed BUN 23 mg/dL, Cr 0.4 mg/dL, AST 743 U/L, ALT 556 U/L, ALP 99 IU/L, and platelets 111/L. He was started on tacrolimus and methylprednisone. On POD 3 he developed an oliguric AKI with Cr to 0.8 mg/dL. He received trials of albumin and diuretics with stability in his renal function; however, he developed progressive ascites. Doppler ultrasound showed normal hepatic vascular flow and venogram was normal. He underwent percutaneous liver biopsy 7 wk post-LT with pathology negative for T cell–mediated rejection but concerning for NRH (Figure 4). At 9 wk post-LT, the patient underwent a transjugular liver biopsy, which demonstrated mild narrowing of his suprahepatic IVC, a portosystemic gradient of 17 mm Hg, and an RA pressure of 9 mm Hg with pathology findings similar to prior. Additional workup for causes of portal hypertension was unrevealing. Because of concern that the patient's mildly narrowed suprahepatic IVC was contributing to his symptoms, he underwent successful IVC angioplasty as well as left hepatic vein angioplasty 12 wk post-LT. His hospitalization was prolonged by difficulty maintaining volume control, and he was discharged home 16 wk post-LT with maintenance diuretics.FIGURE 4.: Posttransplant biopsy for case 4. Posttransplant biopsy for case 4. The donor was a pediatric patient with no pretransplant biopsy performed. A, Reticulin stain showing subtly alternately expanded and compressed hepatic plates, suggestive of NRH (reticulin, ×100). B, Biopsy of posttransplant liver in H&E stain (×100) showing evidence of NRH. H&E, hematoxylin and eosin; NRH, nodular regenerative hyperplasia.DISCUSSION NRH is idiopathic in its origin because it is believed to be a hyperproliferative response to vascular flow abnormalities leading to varying parenchymal perfusion.3,4 Although post-LT portal hypertension resulting from NRH was previously thought to be rare, new data suggest that up to 5.1% of patients post-LT develop NRH leading to CSPH in 25.2% of those patients.5 Yet studies cite the average time from LT to diagnosis of NRH as 6.6 y6 with an average time to the onset of symptoms as 8.4 y5 with no prior cases documenting the diagnosis and development of symptoms as rapidly post-LT as presented here. Although this case series represents a minority of posttransplant patients at our institution with pump parameters (Table 1) comparable with other patient cases, we hypothesize that use of normothermic perfusion pumps combined with patient factors may be linked to the rapid development of posttransplant NRH by contributing to vascular flow abnormalities. Treatment of NRH is typically directed at treating the underlying disorder, with supportive measures for complications from resulting portal hypertension. These patients experienced improvement in portal hypertension symptoms, which is not typical for NRH, suggesting that supportive care, including short-term RRT, may help bridge patients through the most symptomatic period. Data from other transplant centers are needed to determine whether similar clinical cases have occurred elsewhere. Future studies should explore whether perfusion pump use may contribute to NRH development.

The discard of expanded criteria donor (ECD) kidneys is unacceptably high, considering the growing demand for transplantation. Using machine perfusion may reduce the discard rate, increase the number of transplants, and reduce mortality on the waiting list. We developed a 5-y Markov model to simulate incorporating the pulsatile perfusion machine into the current government-funded healthcare system. The model compared the universal use of static cold storage for all kidneys with the selective use of machine perfusion for ECD kidneys. Real-life data were used to compose the cohort characteristics in this model. This pharmacoeconomic analysis aimed to determine the cost-effectiveness and budgetary impact of using machine perfusion to preserve ECD kidneys. Compared with the universal use of static cold storage, the use of machine perfusion for ECD kidneys was associated with an increase in the number of kidney transplants (n = 1123), a decrease in the number of patients on the waiting list (n = 815), and decrease in mortality (n = 120), with a cost difference of US dollar 4 486 009 in the period. The budget impact analysis revealed an additional cost of US dollar 4 453 749 >5 y. The budget impact analysis demonstrated a progressive reduction in costs, becoming cost-saving during the last year of the analysis. This stochastic model showed that incorporating machine perfusion for ECD kidneys is most often a dominant or cost-effective technology associated with an increase in the number of transplants and a reduction in the number of patients on the waiting list, reducing mortality on the waiting list.

Ex situ machine perfusion is increasingly used to preserve and assess donor livers before transplantation. Compared with traditional static cold storage (SCS), machine perfusion exposes livers to an additional risk of microbial contamination. However, information on the risk of microbial transmission during machine perfusion is lacking. All livers that underwent either hypothermic oxygenated machine perfusion (HOPE) or normothermic machine perfusion (NMP) in our center between September 2021 and September 2023, and during which samples were taken from SCS fluid and/or machine perfusion solution for microbiological examination, were included in this retrospective, observational clinical study. Microbial transmission was examined from SCS fluid to machine perfusion solution fluid and, subsequently, to recipients of these livers. A total of 90 cases of liver machine perfusion were included: 59 HOPE and 31 NMP. SCS preservation fluid cultures before HOPE or NMP were positive for at least 1 microorganism in 52% of the cases. After HOPE, there were no cases of positive machine perfusion fluid or evidence of microbial transmission to the recipients. After NMP, in 1 (3%) patient Escherichia coli was grown from abdominal drain fluid, the same bacterial strain that was also grown from the SCS preservation fluid before NMP. This E coli was resistant to the antibiotics that are routinely added to the NMP perfusion fluid. The risk of microbial transmission after machine perfusion is very low but not absent. We recommend routine sampling of machine perfusion fluid at the end of the procedure for microbiological analysis.

Enhanced recovery after surgery (ERAS) pathways represent a comprehensive approach to optimizing perioperative management and reducing hospital stay and cost. In living donor kidney transplantation, key impediments to postoperative discharge include pain, and opioid associated complications such as nausea, vomiting, and the return of gastrointestinal function. In this randomized controlled trial, living kidney transplantation donors were assigned to either the ERAS or control group. The ERAS group patients received 15 preoperative, 17 intraoperative, 19 postoperative element intervention. The control group received standard care. The ERAS group received a multimodal opioid sparing pain management including an intraoperative transverse abdominis plane block. Our primary outcome measure was postoperative opioid consumption. The secondary outcome measures were postoperative pain scores, first oral intake, and hospital length of stay. There were no significant differences in demographics between the 2 groups. The ERAS group had a statistically significant reduction in total postoperative opioid consumption calculated in intravenous morphine equivalents (24.2 ± 20.2 versus 71 ± 39.5 mg, P < 0.01). Postoperative pain scores were significantly lower (P < 0.001) from 1 h postoperatively to 48 h. Surgical time was 45 min shorter (P = 0.037). Intraoperative PlasmaLyte administration was lower (PlasmaLyte: 1444 ± 907 versus 2168 ± 1347 mL, P = 0.049). Time to tolerating regular diet was shorter by 2 h (P < 0.008), and length of hospital stay was decreased by 10.1 h. The ERAS group experienced superior postoperative analgesia and a shorter length of hospital stay compared with controls.

The urinary microbiome, also known as the urobiome, was traditionally considered sterile. However, emerging evidence suggests its presence in the urinary tract. Urobiome dysbiosis has been associated with various urologic conditions, making it a topic of interest also in kidney transplantation. This systematic review examines the evidence of urobiome changes in kidney transplant recipients (KTRs). Systematic literature searches in the PubMed and SCOPUS databases. Of the 770 articles identified, 8 met the inclusion criteria. The urobiome showed reduced diversity in KTRs compared with healthy controls and patients on dialysis. Proteobacteria enrichment was associated with graft stability or spontaneous tolerance in KTRs without immunological events. Kidney interstitial fibrosis and tubular atrophy were associated with changes in resident urinary microbes and increased pathogenic bacteria. Additionally, KTRs with chronic allograft dysfunction had a higher prevalence of Corynebacterium. The review highlights the importance of studying the urobiome in KTRs and its potential impact on transplant outcomes. The field remains largely unexplored, and further research is needed to establish consistent study designs and objectives. Future studies could lead to biomarker discovery, personalized therapies, and improved outcomes and graft survival in KTRs.

Left ventricular hypertrophy (LVH) in patients with end stage renal disease undergoing renal replacement is linked to an increased risk for cardiovascular diseases. Dialysis does not completely prevent or correct this abnormality, and the evidence for kidney transplantation (KT) varies. This analysis aims to explore the relationship between KT and LVH. MEDLINE and Scopus were systematically searched in October 2023. All cross-sectional and longitudinal studies that fulfilled our inclusion criteria were included. Outcome was left ventricular mass index (LVMI) changes. We conducted a meta-analysis using a random effects model. Meta-regression was applied to examine the LVMI changes dependent on various covariates. Sensitivity analysis was used to handle outlying or influential studies and address publication bias. From 7416 records, 46 studies met the inclusion criteria with 4122 included participants in total. Longitudinal studies demonstrated an improvement of LVMI after KT -0.44 g/m2 (-0.60 to -0.28). Blood pressure was identified as a predictor of LVMI change. A younger age at the time of KT and well-controlled anemia were also associated with regression of LVH. In studies longitudinally comparing patients on dialysis and renal transplant recipients, no difference was detected -0.09 g/m2 (-0.33 to 0.16). Meta-regression using changes of systolic blood pressure as a covariate showed an association between higher blood pressure and an increase in LVMI, regardless of the modality of renal replacement treatment. In conclusion, our results indicated a potential cardiovascular benefit, defined as the regression of LVH, after KT. This benefit was primarily attributed to improved blood pressure control rather than the transplantation itself.

MELD 3.0 introduces changes to address waitlist disparities for liver transplant (LT) candidates. Ascites and hepatic encephalopathy (HE) are important milestones in the natural history of cirrhosis regardless of the Model for End-Stage Liver Disease (MELD) score. We aim to assess the impact of ascites and HE and its interaction with MELD 3.0 on waitlist mortality. This is a retrospective study of patients listed for LT in the Organ Procurement and Transplantation Network database from 2016 to 2021. The primary outcome was waitlist mortality (death/delisting for too sick to LT). Ascites/HE were classified as moderate ascites without moderate HE (mAscites), moderate HE without moderate ascites (mHE), both moderate ascites/HE (mBoth), and neither. MELD 3.0 scores were categorized as <20, 20-29, 30-39, and ≥40. Of 39 025 candidates, 29% had mAscites, 3% mHE, and 8% mBoth. One-year waitlist mortality was 30%, 38%, and 47%, respectively, compared with 17% (all P < 0.001) for those with neither. In multivariable Cox regression, the adjusted risk of waitlist mortality associated with mAscites (versus neither) was a hazard ratio (HR) of 1.76 (95% confidence interval [CI], 1.55-2.00) when the MELD 3.0 score was <20, significantly higher than when the MELD 3.0 score was 20-29 (HR 1.40; 95% CI, 1.27-1.54), 30-39 (HR 1.19; 95% CI, 1.04-1.35), and ≥40 (HR 1.14; 95% CI, 0.91-1.43, interaction P < 0.05 for all). A similar pattern was observed by MELD 3.0 for both moderate ascites/HE. The presence of moderate ascites alone, or combined with moderate HE, not only increases the risk of waitlist mortality but also has a differential effect by MELD 3.0, especially at lower MELD scores. Earlier strategies addressing this group and improving treatment plans or access to LT regardless of MELD remain needed.