Simultaneous Liver-kidney Recipients Research Articles

Low-Dose Valganciclovir Prophylaxis Against Cytomegalovirus in Intermediate-Risk Liver and Dual-Abdominal Transplant Recipients.

Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV intermediate-risk liver recipients at 1-year after standard-dose prophylaxis is approximately 5%. However, there are limited data on outcomes after using a "true" low-dose VGC prophylaxis regimen in liver and dual-abdominal transplant recipients as VGC was not dose-adjusted in all patients with impaired renal function in prior studies. The objective was to assess the incidence of CMV associated with low-dose VGC prophylaxis in CMV intermediate-risk liver, simultaneous pancreas-kidney (SPK), and simultaneous liver-kidney (SLK) recipients with creatinine clearance (CrCl) >60 mL/min. This was a retrospective review of CMV intermediate-risk liver, SPK, and SLK recipients with CrCl >60 mL/min transplanted January 2018 to June 2022 who received VGC 450 mg daily for prophylaxis. The primary outcome was incidence of CMV infection 6-months post-transplant. Ninety-nine transplant recipients were included (79 liver, 11 SPK, 9 SLK). The primary outcome occurred in 13% of patients (liver 10%, SPK 36%, SLK 10%), including 1 case of CMV disease and 3 breakthrough infections. In addition, 6 patients experienced CMV infection between 6-months and 1-year. Recurrence occurred in 3 patients. There was no evidence of CMV resistance. Thirty patients experienced neutropenia within 1-year, 32 were prescribed granulocyte-colony stimulating factors, and 5 experienced thrombocytopenia. Two patients died due to graft-vs-host disease. Low-dose VGC prophylaxis led to comparable CMV infection rates at 6-months in CMV intermediate-risk liver and SLK recipients. However, as SPK recipients displayed higher rates of CMV infection, low-dose VGC should be avoided in this population.

Differential in Kidney Graft Years on the Basis of Solitary Kidney, Simultaneous Liver-Kidney, and Kidney-after-Liver Transplants.

The number of simultaneous liver-kidney (SLK) transplants has significantly increased in the United States. There has also been an increase in kidney-after-liver transplants associated with 2017 policy revisions aimed to fairly allocate kidneys after livers. SLK and kidney-after-liver candidates are prioritized in allocation policy for kidney offers ahead of kidney-alone candidates. We compared kidney graft outcomes of kidney-alone transplant recipients with SLK and kidney-after-liver transplants using paired kidney models to mitigate differences among donor risk factors. We evaluated recipient characteristics between transplant types and calculated differential graft years using restricted mean survival estimates. We evaluated 3053 paired donors to kidney-alone and SLK recipients and 516 paired donors to kidney-alone and kidney-after-liver recipients from August 2017 to August 2022. Kidney-alone recipients were younger, more likely on dialysis, and Black race. One-year and 3-year post-transplant kidney graft survival for kidney-alone recipients was 94% and 86% versus SLK recipients 89% and 80%, respectively, P < 0.001. One-year and 3-year kidney graft survival for kidney-alone recipients was 94% and 84% versus kidney-after-liver recipients 93% and 87%, respectively, P = 0.53. The additional kidney graft years for kidney-alone versus SLK transplants was 21 graft years/100 transplants (SEM=5.0) within 4 years post-transplantation, with no significant difference between kidney-after-liver and kidney-alone transplants. Over a 5-year period in the United States, SLK transplantation was associated with significantly lower kidney graft survival compared with paired kidney-alone transplants. Most differences in graft survival between SLK and kidney-alone transplants occurred within the first year post-transplantation. By contrast, kidney-after-liver transplants had comparable graft survival with paired kidney-alone transplants.

Safety and Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Solid Organ Transplant Recipients.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) may be effective in reducing body weight and hemoglobin A1c (HbA1c) post-kidney transplantation. Limited literature exists on use of these agents outside of kidney transplant. The purpose of this program evaluation was to evaluate the safety and efficacy of SGLT2i in kidney, liver, and lung transplant recipients. Methods: This was a retrospective program evaluation of adult kidney, liver, and lung transplant recipients between August 31, 2016 and July 31, 2021. Patients initiated on SGLT2i for diabetes for a minimum of 90 days with at least 1 follow-up appointment were screened for inclusion. Outcomes were compared between SGLT2i initiation to nadir values 3-12-months post-initiation. Outcomes included change in hemoglobin A1c, fasting blood glucose, actual body weight, and body mass index. Safety outcomes included adverse effects, cardiovascular events, death-censored graft loss, and all-cause mortality. Results: Forty-nine patients met inclusion criteria, (26 liver, 18 kidney, 4 lung, and 1 simultaneous liver-kidney recipient). The median time from transplant to SGLT2i initiation was 1216 days (IQR 524-2256). Glycemic and weight loss outcomes showed a statistically significant benefit from SGLT2i use. Total safety outcome incidence was minimal at 12 months. No patient experienced myocardial infarctions, graft loss, or mortality at 3-12 months. One incidence of urinary tract infection and stroke occurred each. The most common adverse effects included hypotension and hypoglycemia. Conclusion: This program evaluation demonstrated that SGLT2i can be used safely in solid organ transplant recipients. These agents can provide an additional non-insulin agent for post-transplant diabetes mellitus management in solid organ transplant.

Infections following rejection therapies in kidney and liver transplant recipients.

Infections are known complications of solid-organ transplant. Treatment for rejection may increase risk of infection. We aimed to study frequency of infection and identify the risk factors for infections in solid organ transplant (SOT) (liver and kidney) recipients treated for rejection. This is a retrospective chart review of all liver and kidney transplant recipients treated for rejection at our institution from 2014 to 2020. We collected information on episodes of acute rejection in the first year of transplant and infections within 6 months following rejection treatment. We identified 257 transplant patients treated for rejection. One hundred twelve (43.6%) developed infections, with a total of 226 infections. Urinary tracts infections were the most common, 72 (31.9%), followed by cytomegalovirus viremia in 37 (16.4%), bacteremia in 24 (10.6%), and BK virus in 14 (6.2%). Female sex (p = .047), elevated neutrophil count at rejection (p = .002), and increased number of rejection episodes (p = .022) were predictors of infection in kidney and simultaneous liver-kidney recipients. No specific type of induction or rejection therapy was identified as a risk factor for infection, likely due to the prophylaxis protocols at our institution. Infection post rejection treatment was associated with higher graft loss (p = .021) and mortality (p = .031) in kidney transplant recipients. Infections are common complications after treatment of SOT rejection. Female gender, higher neutrophil at time of rejection, and increased numbers of rejection episodes were predictors of infections after rejection in simultaneous liver-kidney and kidney transplant patients. Infections were predictors of graft loss at 6 months and mortality at any point in follow-up in kidney transplant patients.

211.16: Effect on Kidney Transplant Allocation With the Implementation of Concentric Circles Liver Allocation Policy: Impact of Simultaneous Liver Kidney Transplantation

Introduction: Although the new acuity circle allocation (ACA) policy has had an improvement in liver transplant (LT) rates in the United States, its effect on other solid organ transplants is unknown. The ACA has likely resulted in institutional and regional changes in the distribution of deceased donor kidneys as well, especially in the setting of simultaneous liver kidney (SLK) transplantation. We sought to review SLK patterns before and after the institution of ACA and determine if SLK rate changes were associated with a change in kidney transplant (KT) rates and patient and graft survival. Methods: Data from the Scientific Registry of Transplant Recipients (SRTR) was analyzed to evaluate rates of SLK transplantation before and after the implementation of ACA. Era 1 was defined as January 1, 2018 to February 3, 2020; Era 2 was defined as February 4, 2020 to June 1, 2021. Statistical comparisons between eras were performed. Transplant programs were divided into high (25%ile), medium (26-74%ile), and low volume (75%ile) KT programs according to Era 1. Similarly, transplant programs were divided into high (25%ile), medium (26-74%ile), and low volume (75%ile) SLK programs according to Era 1. Transplant volume was assessed for Era 2. Results: We analyzed 28,085 SLK and 75,058 KT performed in adult recipients from January 1, 2018 to June 1, 2021; 16,799 SLK and 45,168 KT were performed in Era 1 and 11,286 SLK and 29,890 KT were performed in Era 2. For SLK recipients during Era 1, the 1- and 3-year patient survival was 90.3% and 75.9%, respectively; the 1- and 3-year graft survival was 97.4% and 96.8%, respectively. During Era 2, the 1-year patient and graft survival for SLK recipients was 85.8% and 97.5%, respectively. For KT recipients during Era 1, the 1- and 3-year patient survival was 97.1% and 87.6%, respectfully; graft survival was 97.5% and 93.1%, respectively. During Era 2, the 1-year patient and graft survival for KT recipients was 93.2% and 96.9%, respectively. As a result of ACA, 1,008 additional kidneys went to SLK recipients. Changes in volume were most evident for low-volume SLK centers with an increase of 8 additional transplants, medium-volume SLK centers (increase of 1.2) and high-volume centers (increase of 4.6); while KT programs generally lost KT with low-volume KT centers with a decrease of 1.7 transplants, medium-volume KT centers (decrease of 1.5) and high-volume centers (decrease of 67). Conclusion: The institution of the ACA led to differing acceptance practices for SLK recipients with a net efflux of kidneys from solitary KT recipients. Interestingly, patient survival decreased while graft survival improved for SLK recipients while both patient and graft survival decreased for KT as a result of ACA.

Long-term outcomes of crossmatch positive simultaneous liver-kidney transplantations in the United States.

The long-term outcomes of positive crossmatch (+XM) simultaneous liver-kidney (SLK) transplantations are conflicting. We examined the association between crossmatch status and SLK outcomes in recipients discharged on tacrolimus and mycophenolate with or without steroids. We analyzed the Scientific Registry of Transplant Recipients for all primary SLK recipients between 2003 and 2020 with available crossmatch and induction data. We grouped recipients according to the crossmatch status: negative crossmatch (-XM; n=3040) and +XM (n=407). Kaplan-Meier curves were generated to examine recipient, death-censored liver, and death-censored kidney survival by crossmatch status. Cox proportional hazard models were used to investigate the association between crossmatch status and outcomes of interest with follow-up censored at 10 years. Models were adjusted for recipient age, sex, diabetes mellitus, Model for End-Stage Liver Disease score, duration on the liver waiting list, induction immunosuppression, steroid maintenance, hepatitis C infection, donor age and sex, local vs. shared organ, cold ischemia time, and previous liver transplantation status. In the univariable analysis, crossmatch status was not associated with recipient survival (log-rank p=0.63), death-censored liver graft survival (log-rank p=0.05), or death-censored kidney graft survival (log-rank p=0.11). Compared with -XM, +XM recipients had a similar 1-year liver rejection rate, but higher kidney rejection rate (4.6% vs. 8.9%, p=0.002). In the multivariable models, +XM status was not associated with deleterious long-term recipient, liver, or kidney grafts survival. -XM and +XM SLK transplantations have comparable long-term recipient, liver graft, and kidney survival with a slightly increased risk of early kidney allograft rejection in the +XM group. Crossmatch positivity in SLK transplantations should not influence the decision to use organs from a specific donor.

The changing impact of pre-liver transplant renal dysfunction on post-transplant survival: results of 2 decades from a single center

Introduction and ObjectivesRenal dysfunction before liver transplantation (LT) is associated with higher post-LT mortality. We aimed to study if this association still persisted in the contemporary transplant era. Materials and MethodsWe retrospectively reviewed data on 2871 primary LT performed at our center from 1998 to 2018. All patients were listed for LT alone and were not considered to be simultaneous liver–kidney (SLK) transplant candidates. SLK recipients and those with previous LT were excluded. Patients were grouped into 4 eras: era-1 (1998–2002, n = 488), era-2 (2003–2007, n = 889), era-3 (2008–2012, n = 703) and era-4 (2013–2018, n = 791). Pre-LT renal dysfunction was defined as creatinine (Cr) >1.5 mg/dl or on dialysis at LT. The effect of pre-LT renal dysfunction on post-LT patient survival in each era was examined using Kaplan Meier estimates and univariate and multivariate Cox proportional hazard analyses. ResultsPre-LT renal dysfunction was present in 594 (20%) recipients. Compared to patients in era-1, patients in era-4 had higher Cr, lower eGFR and were more likely to be on dialysis at LT (P < 0.001). Pre-LT renal dysfunction was associated with worse 1, 3 and 5-year survival in era-1 and era-2 (P < 0.005) but not in era-3 or era-4 (P = 0.13 and P = 0.08, respectively). Multivariate analysis demonstrated the lack of independent effect of pre-LT renal dysfunction on post-LT mortality in era-3 and era-4. A separate analysis using eGFR <60 mL/min/1.73 m2 at LT to define renal dysfunction showed similar results. ConclusionsPre-LT renal dysfunction had less impact on post-LT survival in the contemporary transplant era.

And Then There Were Three: Effects of Pretransplant Dialysis on Multiorgan Transplantation.

Background.Simultaneous liver-kidney (SLK) and simultaneous heart-kidney (SHK) transplantation currently utilize 6% of deceased donor kidneys in the United States. To what extent residual kidney function accounts for apparent kidney allograft survival is unknown.Methods.We examined all adult SLK and SHK transplants in the United States during 1995–2014. We considered the duration of dialysis preceding SLK or SHK (≥90 d, 1–89 d, or none) as a proxy of residual kidney function. We used multinomial logistic regression to estimate the difference in the adjusted likelihood of 6- and 12-month apparent kidney allograft failure between the no dialysis versus ≥90 days dialysis groups.Results.Of 4875 SLK and 848 SHK recipients, 1775 (36%) SLK and 449 (53%) SHK recipients received no dialysis before transplant. The likelihood of apparent kidney allograft failure was 1%–3% lower at 12 months in SLK and SHK recipients who did not require pretransplant dialysis relative to recipients who required ≥90 days of pretransplant dialysis. Among 3978 SLK recipients who survived to 1 year, no pretransplant dialysis was associated with a lower risk of apparent kidney allograft failure over a median follow-up of 5.7 years (adjusted hazard ratio 0.73 [0.55–0.96]).Conclusions.Patients with residual kidney function at the time of multiorgan transplantation are less likely to have apparent failure of the kidney allograft. Whether residual kidney function facilitates function of the allograft or whether some SLK and SHK recipients have 3 functional kidneys is unknown. Sustained kidney function after SLK and SHK transplants does not necessarily indicate successful MOT.

Steroid-sparing maintenance immunosuppression is safe and effective after simultaneous liver-kidney transplantation.

Optimization of maintenance immunosuppression (mIS) regimens in the transplant recipient requires a balance between sufficient potency to prevent rejection and avoidance of excessive immunosuppression to prevent toxicities and complications. The optimal regimen after simultaneous liver-kidney (SLK) transplantation remains unclear, but small single-center reports have shown success with steroid-sparing regimens. We studied 4184 adult SLK recipients using the Scientific Registry of Transplant Recipients, from March 1, 2002, to February 28, 2017, on tacrolimus-based regimens at 1year post-transplant. We determined the association between mIS regimen and mortality and graft failure using Cox proportional hazard models. The use of steroid-sparing regimens increased post-transplant, from 16.1% at discharge to 88.0% at 5years. Using multi-level logistic regression modeling, we found center-level variation to be the major contributor to choice of mIS regimen (ICC 44.5%; 95% CI: 36.2%-53.0%). In multivariate analysis, use of a steroid-sparing regimen at 1year was associated with a 21% decreased risk of mortality compared to steroid-containing regimens (aHR 0.79, P=.01) and 20% decreased risk of liver graft failure (aHR 0.80, P=.01), without differences in kidney graft loss risk (aHR 0.92, P=.6). Among SLK recipients, the use of a steroid-sparing regimen appears to be safe and effective without adverse effects on patient or graft survival.

Liver Transplantation in Patients With Pretransplant Renal Dysfunction: A "Safety Net" Is in Place, but Who Should Walk the Tightrope?

Liver Transplantation in Patients With Pretransplant Renal Dysfunction: A "Safety Net" Is in Place, but Who Should Walk the Tightrope?

Delayed Graft Function in Simultaneous Liver Kidney Transplantation.

Delayed graft function (DGF) is associated with inferior posttransplant outcomes in kidney transplantation. Given these adverse outcomes, we sought to determine the incidence, unique risk factors, and posttransplant outcomes for simultaneous liver kidney (SLK) transplant recipients developing DGF. We studied 6214 adult SLK recipients from March 2002 to February 2017 using the Scientific Registry of Transplant Recipients. We determined associations between risk factors and DGF using Poisson multivariate regression and between DGF and graft failure and mortality using Cox proportional hazard analysis. The overall rate of DGF was 21.8%. Risk factors for DGF in the hepatitis C virus (HCV)-negative recipient population included pretransplant dialysis (adjusted incident rate ratio [aIRR] 3.26, P = 0.004), donor body mass index (aIRR 1.25 per 5 kg/m, P = 0.01), and transplantation with a donation after circulatory death (aIRR 5.38, P = 0.001) or imported donor organ (regional share aIRR 1.69, P = 0.03; national share aIRR 4.82, P < 0.001). DGF was associated with a 2.6-fold increase in kidney graft failure (adjusted hazard ratio [aHR] 2.63, P < 0.001), 1.6-fold increase in liver graft failure (aHR 1.62, P < 0.001), and 1.6-fold increase in mortality (aHR 1.62, P < 0.001). In HCV-negative SLK recipients, recipient pretransplant dialysis and components of kidney graft quality comprise significant risk factors for DGF. Regardless of HCV status, DGF is associated with inferior posttransplant outcomes. Understanding these risk factors during clinical decision-making may improve prevention of DGF and may represent an opportunity to improve posttransplant outcomes.

Graft quality matters: Survival after simultaneous liver-kidney transplant according to KDPI.

Poor renal function is associated with higher mortality after liver transplantation. Our aim was to understand the impact of kidney graft quality according to the kidney donor profile index (KDPI) score on survival after simultaneous liver-kidney (SLK) transplantation. Using United Network of Organ Sharing data from 2002 to 2013 for adult deceased donor SLK recipients, we compared survival and renal graft outcomes according to KDPI. Of 4207 SLK transplants, 6% were from KDPI >85% donors. KDPI >85% recipients had significantly increased mortality (HR=1.83, 95%CI=1.44-2.31) after adjusting for recipient factors. Additionally, dialysis in the first week (HR=1.4, 95%CI=1.2-1.7) and death-censored kidney graft failure at 1year (HR=5.7, 95%CI=4.6-7.0) were associated with increased mortality after adjusting for recipient factors and liver donor risk index score. KDPI >85% recipients had worse patient and graft survival after SLK. Poor renal allograft outcomes including dialysis in the first week and death-censored kidney graft failure at 1year, which occurred more frequently with KDPI >85% grafts, were associated with significantly reduced patient survival. Questions remain about the survival impact of liver vs kidney graft quality given the close relationship between donor factors contributing to both, but KDPI can still be valuable as a metric readily available at the time of organ offers for SLK candidates.

Utility in Treating Kidney Failure in End-Stage Liver Disease With Simultaneous Liver-Kidney Transplantation.

BackgroundSimultaneous liver-kidney (SLK) transplantation plays an important role in treating kidney failure in patients with end-stage liver disease. It used 5% of deceased donor kidney transplanted in 2015. We evaluated the utility, defined as posttransplant kidney allograft lifespan, of this practice.MethodsUsing data from the Scientific Registry of Transplant Recipients, we compared outcomes for all SLK transplants between January 1, 1995, and December 3, 2014, to their donor-matched kidney used in kidney-alone (Ki) or simultaneous pancreas kidney (SPK) transplants. Primary outcome was kidney allograft lifespan, defined as the time free from death or allograft failure. Secondary outcomes included death and death-censored allograft failure. We adjusted all analyses for donor, transplant, and recipient factors.ResultsThe adjusted 10-year mean kidney allograft lifespan was higher in Ki/SPK compared with SLK transplants by 0.99 years in the Model for End-stage Liver Disease era and 1.71 years in the pre-Model for End-stage Liver Disease era. Death was higher in SLK recipients relative to Ki/SPK recipients: 10-year cumulative incidences 0.36 (95% confident interval 0.33-0.38) versus 0.19 (95% confident interval 0.17-0.21).ConclusionsSLK transplantation exemplifies the trade-off between the principles of utility and medical urgency. With each SLK transplantation, about 1 year of allograft lifespan is traded so that sicker patients, that is, SLK transplant recipients, are afforded access to the organ. These data provide a basis against which benefits derived from urgency-based allocation can be measured.

Loss of Pediatric Kidney Grafts During the “High–Risk Age Window”: Insights From Pediatric Liver and Simultaneous Liver–Kidney Recipients

Pediatric kidney transplant recipients experience a high-risk age window of increased graft loss during late adolescence and early adulthood that has been attributed primarily to sociobehavioral mechanisms such as nonadherence. An examination of how this age window affects recipients of other organs may inform the extent to which sociobehavioral mechanisms are to blame or whether kidney-specific biologic mechanisms may also exist. Graft loss risk across current recipient age was compared between pediatric kidney (n = 17,446), liver (n = 12,161) and simultaneous liver-kidney (n = 224) transplants using piecewise-constant hazard rate models. Kidney graft loss during late adolescence and early adulthood (ages 17-24 years) was significantly greater than during ages <17 (aHR = 1.79, 95%CI = 1.69-1.90, p < 0.001) and ages >24 (aHR = 1.11, 95%CI = 1.03-1.20, p = 0.005). In contrast, liver graft loss during ages 17-24 was no different than during ages <17 (aHR = 1.03, 95%CI = 0.92-1.16, p = 0.6) or ages >24 (aHR = 1.18, 95%CI = 0.98-1.42, p = 0.1). In simultaneous liver-kidney recipients, a trend towards increased kidney compared to liver graft loss was observed during ages 17-24 years. Late adolescence and early adulthood are less detrimental to pediatric liver grafts compared to kidney grafts, suggesting that sociobehavioral mechanisms alone may be insufficient to create the high-risk age window and that additional biologic mechanisms may also be required.

Loss of Pediatric Kidney Grafts During the “High–Risk Age Window”: Insights From Pediatric Liver and Simultaneous Liver–Kidney Recipients

Loss of Pediatric Kidney Grafts During the “High–Risk Age Window”: Insights From Pediatric Liver and Simultaneous Liver–Kidney Recipients

Incidence and impact of rejection following simultaneous liver-kidney transplantation

Due to hepatic immunoregulation, simultaneous liver-kidney recipients are presumed to be reasonably protected from kidney rejection and typically receive less immunosuppression compared to kidney transplants alone. However, data to support these conclusions and practices are sparse. We characterized the incidence and types of rejection, graft function, and graft and patient survival in a large population of simultaneous liver-kidney recipients (n=140) with long-term follow-up at our centre (1998-2010). Acute cellular, antibody-mediated, and chronic kidney rejection was diagnosed in 9 (6.4%), 2 (1.4%), and 1 (0.7%) patient, respectively. Borderline acute kidney rejection was diagnosed in another 16 patients (11.4%). Acute cellular liver rejection occurred in 16 (11.4%) and chronic liver rejection in 4 (2.9%). One-, three-, and five-year patient survival was 86.4%, 78.0%, and 74.0%, respectively, and did not significantly differ by presence or absence of kidney or liver rejection. However, kidney rejection was associated with decreased renal function by lower serum GFR over time (p=0.003). Various forms of kidney rejection occurred in ∼20% of our simultaneous liver-kidney recipients and were associated with deterioration in graft function, indicating that the liver may not confer complete protective allo-immunity. More stringent graft monitoring and management strategies, perhaps more akin to kidney transplant alone, should be prospectively studied in simultaneous liver-kidney recipients.

Simultaneous Liver-Kidney Transplants - The Argument for Standardized Allocation Rules.

Background. There are currently minimal allocation rules for simultaneous liver-kidney (SLK) transplants (txs) and a lack of standardized allocation rules for these txs may be diverting donated kidneys (KIs) from candidates in medical need to those who could regain KI function with a solitary liver (LI) tx. The Organ Procurement and Transplantation Network (OPTN) KI Committee is in the early stages of considering a policy proposal to address SLK allocation. This abstract is to inform the tx community of the need for equitable allocation rules for SLK txs. Data. The OPTN database was analyzed for clinical/donor characteristics of SLK txs and KI listings after LI txs to determine the number of recipients who had clinical factors that suggest they may not have needed the KI at time of LI tx. Results. During 1/1/05-6/30/13, 510 (15%) of 3,431 SLK recipients did not receive pre-tx dialysis and had a serum creatinine of <2.5 mg/dl at tx, which suggests that some of these patients may not have needed the KI. Of these 510 SLK txs, 237 (47%) had a Kidney Donor Profile (KDPI) of <35%. Among recipients of solitary LI tx, on average 200 patients are listed for a KI tx after LI tx yearly. The median time to listing for these patients was 9 yrs for those with a KI diagnosis of CNI toxicity, 6.5 yrs for hypertension, and 5 yrs for diabetes; additionally, only 19% were listed within a year of the LI tx. Summary. These findings suggest that approximately 500, or 60 SLK recipients per year, may not have needed the KI. They also suggest that the fear of chronic KI insufficiency rapidly leading to ESRD after LI tx for a large number of solitary LI patients may be unfounded. KIs utilized in SLK txs also tend to have a lower KDPI score, suggesting that the lack of standardized clinical criteria for SLK txs will, in the new kidney allocation system, divert some KIs away from pediatric candidates and adults with estimated post-tx survival (EPTS) scores in the top 20%. The Committee continues to review data and discuss new SLK allocation policy to achieve equity and best use of donated organs as specified in the Final Rule.

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Aim Donor specific HLA antibodies (DSA) in liver transplant recipients have been associated with allograft dysfunction. This analysis aims to describe the clinical outcomes in simultaneous liver-kidney (SLK) recipients with and without HLA antibodies. Methods A retrospective review of 50 SLK recipients transplanted from 03/2010 to 03/2013 identified 31 patients with pre- and post-transplant HLA testing and donor HLA typing. HLA antibodies were monitored by Flow PRA and Luminex single antigen assays. Results The 31 SLK recipients evaluated were 58 ± 10 years old at transplant, had a MELD score of 38 ± 5, were primarily male (52%), Caucasian (68%), on dialysis (81%), and had liver disease due to hepatitis C and/or alcoholic cirrhosis (65%). Mean follow-up was 11 ± 8 mos. Sensitization and clinical outcomes are described in the figure. Flow crossmatch (FXM) was performed on pre-transplant sera in 14 patients. Two sensitized patients without a DSA evaluation had a negative FXM. In DSA+ patients, 11 of 12 FXM were positive. DSA became negative post-transplant in 54% of pre-transplant DSA+ patients. De novo DSA developed in 17% of unsensitized patients. Acute cellular (ACR) or antibody mediated rejection of the kidney were most common in sensitized patients, with the majority seen in DSA+ patients. Liver ACR was seen in 1 unsensitized and 1 DSA+ patient. Three deaths occurred in DSA+ patients.[Fig. 1] Conclusions DSA levels may decrease post-transplant in some patients; however, persistent DSA post-transplant increases likelihood of rejection. Further prospective analysis of DSA in SLK recipients will be important to determine the role of DSA in allograft survival. Download full-size image

Renal dysfunction and the liver transplant recipient; novel strategies for determination of reversibility and renal protective therapies pretransplant and posttransplant

Renal dysfunction is one of the most common and important complications in liver transplant candidates and recipients. Recent publications have highlighted important developments in this field. Inclusion of the serum creatinine in the Model for Endstage Liver Disease (MELD) score has led to an increased number of liver transplant candidates and recipients with renal dysfunction. The development of posttransplant renal dysfunction negatively impacts patient survival. Therefore, the careful identification of appropriate candidates for simultaneous liver-kidney (SLK) transplant is critical. Recent publications have helped in the appropriate selection of SLK recipients. One of the most important strategies to help mitigate renal dysfunction in liver transplant recipients is the careful management of immunosuppression. Important contributing factors to posttransplant renal dysfunction include pretransplant renal disease and immunosuppression, namely calcineurin inhibitors (CNIs). One of the most effective means of preventing posttransplant renal failure is observation of the defined criteria for selecting patients for SLK. In addition, avoidance and minimization of CNIs may help to mitigate posttransplant renal disease.

Kidney Allocation to Liver Transplant Candidates with Renal Failure of Undetermined Etiology: Role of Percutaneous Renal Biopsy

The feasibility, value and risk of percutaneous renal biopsy (PRB) in liver transplant candidates with renal failure are unknown. PRB was performed on 44 liver transplant candidates with renal failure of undetermined etiology and glomerular filtration rate (GFR) <40 mL/min/1.73 m(2) (n = 37) or on renal replacement therapy (RRT) (n = 7). Patients with >or=30% interstitial fibrosis (IF), >or=40% global glomerulosclerosis (gGS) and/or diffuse glomerulonephritis were approved for simultaneous-liver-kidney (SLK) transplantation. Prebiopsy GFR, urinary sodium indices, dependency on RRT and kidney size were comparable between 27 liver-transplant-alone (LTA) and 17 SLK candidates and did not relate to the biopsy diagnosis. The interobserver agreement for the degree of IF or gGS was moderate-to-excellent. After a mean of 78 +/- 67 days, 16 and 8 patients received LTA and SLK transplants. All five LTA recipients on RRT recovered kidney function after transplantation and serum creatinine was comparable between LTA and SLK recipients at last follow-up. Biopsy complications developed in 13, of these, five required intervention. PRB is feasible in liver transplant candidates with renal failure and provides reproducible histological information that does not relate to the pretransplant clinical data. Randomized studies are needed to determine if PRB can direct kidney allocation in this challenging group of liver transplant candidates.