Liver Transplantation as a Treatment for Unresectable Hepatic Adenoma in a Patient With Abernethy Syndrome.

Abernethy syndrome is a rare congenital anomaly characterized by an intrahepatic or extrahepatic portosystemic shunt. Most patients are asymptomatic; however, due to the alteration in, or lack of, a portovenous flow, patients with Abernethy syndrome are at high risk of developing sequelae of liver failure. Once these complications develop, the only definitive treatment is transplantation. Patients with Abernethy syndrome are also at a higher risk of developing benign and malignant liver lesions, including hepatic adenomas. Here, we describe the first case of deceased donor liver transplantation as a treatment for a patient with type 1 Abernethy syndrome complicated by large, unresectable hepatic adenoma, found to have focal hepatocellular carcinoma on pathologic examination. Our male patient was found to have elevated liver enzymes at age 33, during a routine outpatient medical appointment. Despite being asymptomatic, his history of prior liver resection prompted CT imaging, which revealed two large liver lesions concerning for hepatic adenomas. When surveillance imaging showed a significant growth of the liver lesions, biopsy was pursued, which confirmed a diagnosis of hepatic adenomas. However, given the size of these lesions, resection was not a viable option for the patient. Instead, the patient underwent liver transplantation at age 41, which he tolerated well. Our case demonstrates the utility of deceased donor liver transplantation as a treatment for patients with Abernethy syndrome complicated by unresectable adenomas.

Successful Treatment of Tenofovir Alafenamide-Induced Lactic Acidosis: A Case Report.

Nucleoside or nucleotide analogues (NAs) have the potential to cause lactic acidosis by inhibiting DNA polymerase-γ of human mitochondria and impairing aerobic metabolism. Patients may be asymptomatic, have mild non-specific symptoms, or present in multisystem organ failure. There is a paucity of data to guide management of life-threatening lactic acidosis due to NA therapy. Here we describe a case of a 60-year old critically ill male with decompensated cirrhosis secondary to hepatitis B virus (HBV) infection who developed severe lactic acidosis (13.8 mmol/L) 2 days after initiation of tenofovir alafenamide (TAF). All other possible etiologies for the elevated lactate were ruled out. Lactic acidosis resolved rapidly with TAF discontinuation and supplementation with cofactors supporting mitochondrial oxidative phosphorylation, including coenzyme Q10, levocarnitine, riboflavin, and thiamine. This case highlights the ability of TAF to cause lactic acidosis early after therapy initiation, especially in susceptible hosts, and reviews the potential role for cofactor supplementation for drug-induced mitochondrial injury.

Clinical and Financial Implications of 2 Treatment Strategies for Donor-derived Hepatitis C Infections.

Transplanting hepatitis C viremic donor organs into hepatitis C virus (HCV)-negative recipients is becoming increasingly common; however, practices for posttransplant direct-acting antiviral (DAA) treatment vary widely. Protracted insurance authorization processes for DAA therapy often lead to treatment delays. METHODS: At our institution, 2 strategies for providing DAA therapy to HCV- recipients of HCV+ transplants have been used. For thoracic organ recipients, an institution-subsidized course of initial therapy was provided to ensure an early treatment initiation date. For abdominal organ recipients, insurance approval for DAA coverage was sought once viremia developed, and treatment was initiated only once the insurance-authorized supply of drug was received. To evaluate the clinical impact of these 2 strategies, we retrospectively collected data pertaining to the timing of DAA initiation, duration of recipient viremia, and monetary costs incurred by patients and the institution for patients managed under these 2 DAA coverage strategies. RESULTS: One hundred fifty-two transplants were performed using HCV viremic donor organs. Eighty-nine patients received DAA treatment without subsidy, and 62 received DAA treatment with subsidy. One patient who never developed viremia posttransplant received no treatment. Subsidizing the initial course enabled earlier treatment initiation (median, 4 d [interquartile range (IQR), 2-7] vs 10 [IQR, 8-13]; P < 0.001) and shorter duration of viremia (median, 16 d [IQR, 12-29] vs 36 [IQR, 30-47]; P < 0.001). Institutional costs averaged $9173 per subsidized patient and $168 per nonsubsidized patient. Three needlestick exposures occurred in caregivers of viremic patients. CONCLUSIONS: Recipients and their caregivers stand to benefit from earlier DAA treatment initiation; however, institutional costs to subsidize DAA therapy before insurance authorization are substantial. Insurance authorization processes for DAAs should be revised to accommodate this unique patient group.

Comparison of Non-Tumoral Portal Vein Thrombosis Management in Cirrhotic Patients: TIPS Versus Anticoagulation Versus No Treatment.

BACKGROUND: There is a lack of consensus in optimal management of portal vein thrombosis (PVT) in patients with cirrhosis. The purpose of this study is to compare the safety and thrombosis burden change for cirrhotic patients with non-tumoral PVT managed by transjugular intrahepatic portosystemic shunt (TIPS) only, anticoagulation only, or no treatment. METHODS: This single-center retrospective study evaluated 52 patients with cirrhosis and non-tumoral PVT managed by TIPS only (14), anticoagulation only (11), or no treatment (27). The demographic, clinical, and imaging data for patients were collected. The portomesenteric thrombosis burden and liver function tests at early follow-up (6-9 months) and late follow-up (9-16 months) were compared to the baseline. Adverse events including bleeding and encephalopathy were recorded. RESULTS: The overall portomesenteric thrombosis burden improved in eight (72%) TIPS patients, three (27%) anticoagulated patients, and two (10%) untreated patients at early follow-up (p = 0.001) and in seven (78%) TIPS patients, two (29%) anticoagulated patients, and three (17%) untreated patients in late follow-up (p = 0.007). No bleeding complications attributable to anticoagulation were observed. CONCLUSION: TIPS decreased portomesenteric thrombus burden compared to anticoagulation or no treatment for cirrhotic patients with PVT. Both TIPS and anticoagulation were safe therapies.

Cholangiopathy After Severe COVID-19: Clinical Features and Prognostic Implications.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging. METHODS: We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database. RESULTS: Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation. DISCUSSION: Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.

Pancreas transplantation from hepatitis C viremic donors to uninfected recipients.

Despite utilization of hepatitis C viremic organs for hepatitis C naïve recipients (HCV D+/R-) in other solid organ transplants, HCV viremic pancreata remain an unexplored source of donor organs. This study reports the first series of HCV D+/R- pancreas transplants. HCV D+/R- had shorter waitlist times compared to HCV D-/R-, waiting a mean of 16 days from listing for HCV-positive organs. HCV D+/R- had a lower match allocation sequence than HCV D-/R-, and this correlated with receipt of organs with a lower Pancreas Donor Risk Index (PDRI) score. All HCV D+/R- had excellent graft function with a mean follow-up of 438 days and had undetectable HCV RNA levels by a mean of 23 days after initiation of HCV-directed therapy. The rates of infectious complications, reoperation, readmission, rejection, and length of stay were not impacted by donor HCV status. A national review of potential ideal pancreas donors found that 37% of ideal HCV-negative pancreas allografts were transplanted, compared to only 5% of ideal HCV-positive pancreas allografts. The results of the current study demonstrate the safety of accepting HCV-positive pancreata for HCV-naïve recipients and advocates for increased utilization of ideal HCV-positive pancreas allografts.

Hepatic Artery Microvascular Anastomosis in Liver Transplantation: A Systematic Review of the Literature.

BACKGROUND: The operating microscope is used in many centers for microvascular hepatic arterial reconstruction in living as well as deceased donor liver transplantation in adult and pediatric recipients. To date, a systematic review of the literature examining this topic is lacking. METHODS: This systematic review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Three different electronic databases (PubMed, Embase OVID, and Cochrane CENTRAL) were queried. RESULTS: A total of 34 studies were included. The rate of hepatic artery thrombosis (HAT) in noncomparative studies (28) ranged from 0% to 10%, with 8 studies reporting patient deaths resulting from HAT. Within comparative studies, the rate of HAT in patients who underwent arterial reconstruction using the operating microscope ranged from 0% to 5.3%, whereas the rate of HAT in patients who underwent arterial reconstruction using loupe magnification ranged from 0% up to 28.6%, and 2 studies reported patient deaths resulting from HAT. Two comparative studies did not find statistically significant differences between the 2 groups. CONCLUSIONS: Our comprehensive systematic review of the literature seems to suggest that overall, rates of HAT may be lower when the operating microscope is used for hepatic arterial reconstruction in liver transplantation. However, matched comparisons are lacking and surgical teams need to be mindful of the learning curve associated with the use of the operating microscope as compared with loupe magnification, as well as the logistical and time constraints associated with setup of the operating microscope.

Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma.

PURPOSE: To investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A-B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses. RESULTS: The median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6-11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1-3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9-23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6-26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2-7.2), and progression-free survival was 5.7 months (95% CI, 4.3-7.1). CONCLUSIONS: Radioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.

IdeS (Imlifidase): A Novel Agent That Cleaves Human IgG and Permits Successful Kidney Transplantation Across High-strength Donor-specific Antibody.

OBJECTIVES: The presence of a donor-specific positive crossmatch has been considered to be a contraindication to kidney transplantation because of the risk of hyperacute rejection. Desensitization is the process of removing hazardous preformed donor-specific antibody (DSA) in order to safely proceed with transplant. Traditionally, this involves plasmapheresis and intravenous immune globulin treatments that occur over days to weeks, and has been feasible when there is a living donor and the date of the transplant is known, allowing time for pre-emptive treatments. For sensitized patients without a living donor, transplantation has been historically difficult. SUMMARY OF BACKGROUND DATA: IdeS (imlifidase) is an endopeptidase derived from Streptococcus pyogenes which has specificity for human IgG, and when infused intravenously results in rapid cleavage of IgG. METHODS: Here we present our single-center's experience with 7 highly sensitized (cPRA98-100%) kidney transplant candidates who had DSA resulting in positive crossmatches with their donors (5 deceased, 2 living) who received IdeS within 24 hours prior to transplant. RESULTS: All pre-IdeS crossmatches were positive and would have been prohibitive for transplantation. All crossmatches became negative post-IdeS and the patients underwent successful transplantation. Three patients had DSA rebound and antibody-mediated rejection, which responded to standard of care therapies. Three patients had delayed graft function, which ultimately resolved. No serious adverse events were associated with IdeS. All patients have functioning renal allografts at a median follow-up of 235 days. CONCLUSION: IdeS may represent a groundbreaking new method of desensitization for patients who otherwise might have no hope for receiving a lifesaving transplant.

Surgical approach, cost, and complications of appendectomy in kidney transplant recipients.

Kidney transplant recipients (KTRs) have greater morbidity and length of stay (LOS) following certain surgical procedures than non-KTR. Given that appendectomy is one of the most common surgical procedures, we investigated differences in outcomes between 1336 KTR and 2 640 247 non-KTR postappendectomy at transplant and nontransplant centers in the United States from 2000 to 2011, using NIS data and adjusting for patient-level and hospital-level factors. Postoperative complications were identified using ICD-9 codes. Among KTR, there were no post-appendectomy in-hospital deaths, compared to a 0.2% in non-KTR (P = .5). Overall complications were similar among KTR and non-KTR (17.0% vs 11.6%; aOR:0.77 1.121.61 ). LOS and costs were greater for KTR compared to non-KTR (LOS ratio 1.19 1.311.45 ; cost ratio 1.11 1.171.26 ). Only 44.8% of KTR had laparoscopic approach compared to 54.5% of non-KTR, but had similar complication rates (10.6 vs 8.7%, P = .5). When treated at transplant centers, KTR had similar complications (aOR 0.44 0.791.43 ), but longer LOS (ratio 1.21 1.371.55 ) and greater hospital-associated costs (ratio 1.19 1.291.41 ) than non-KTR. Conversely, at nontransplant centers, KTR and non-KTR had similar complications (aOR 0.75 1.232.0 ), LOS (ratio 0.84 0.961.09 ), and cost (ratio 0.93 1.011.10 ). Contrary to other procedures, KTR did not constitute a high-risk group for patients undergoing appendectomy.

Nontraditional sites for vascular anastomoses to enable kidney transplantation in patients with major systemic venous thromboses.

Successful renal transplantation requires low-pressure venous drainage to permit adequate outflow from the allograft. We report here a series of three patients in whom the inferior vena cava as well as bilateral iliac veins were thrombosed, making it necessary to explore less traditional vessels for venous drainage of the renal allograft. We utilized the splanchnic vasculature in two cases and the native left renal vein in another. The resulting atypical intra-abdominal locations of these allografts also presented difficulties for arterial anastomoses and for urinary drainage. Arterial conduits were utilized in two cases to facilitate anastomosis to the common iliac artery or the aorta, and in the third case, the splenic artery was used for arterial inflow. A traditional ureterocystostomy was technically feasible for only one patient. In another, ureteroureterostomy to the native ureter was performed, and in the third case, the creation of an ileal conduit was necessary. All three patients had antibodies to human leukocyte antigens and two required desensitization. All three kidneys had immediate graft function and continued to function at 1 year post-transplant. With a combination of planning, creativity, and persistence, patients with IVC thrombosis can enjoy the benefits of renal transplantation.

Single-Center Experience in Pre-transplant Hepatitis C Virus (HCV) Treatment Among Living Donor Liver Transplant Candidates: Bridging the Direct-Acting Antivirals (DAA).

BACKGROUND Treatment with DAAs before deceased donor liver transplantation has been shown to be an effective strategy to prevent post-transplant HCV recurrence, with a 95% cure-rate among individuals who achieve undetectable HCV VL for ≥30 days pre- transplant. This strategy has not been evaluated in LDLT. MATERIAL AND METHODS We evaluated outcomes in LDLT recipients treated with DAAs pre-transplant and bridged with 4 weeks of post-transplant SOF. All cases of LDLT at Johns Hopkins (1/1/2014-3/1/15) were retrospectively reviewed. RESULTS There were 4 HCV+ LDLT cases treated with DAAs pre- and post-transplant. Pre-transplant DAA regimens included SOF plus SIM in 2 cases of HCC and SOF plus RBV in 2 cases of ESLD. All patients achieved negative VL by week 7 of treatment and all patients had at least 30 days of HCV RNA negativity at the time of LDLT. Patient 4 had a delay in LDLT due to uncontrolled pulmonary hypertension, and experienced viral breakthrough because of treatment interruption. Due to concerns for SOF resistance, a salvage regimen of LDV-SOF and SIM was used. Post-LDLT patients 1-3 received 4 weeks of SOF monotherapy and patient 4 received 14 weeks of LDV-SOF. Three patients achieved SVR12. One died from non-HCV related complications at 4 months post-LDLT. CONCLUSIONS Our preliminary experience suggests that bridging DAAs pre- and post-LDLT is an effective strategy to prevent HCV recurrence. With delays in transplant and prolonged use of SOF/RBV, there is a risk of viral breakthrough, but a salvage strategy of triple DAA therapy can be effective.

Current management of liposarcoma of the spermatic cord: A case report and review of the literature.

Liposarcomas of the spermatic cord, a rare cause of an inguinal mass, may closely mimic inguinal hernias on clinical examination. However, these tumors require a different surgical approach and treatment plan; therefore, intraoperative diagnosis might complicate patient management. We report the case of a 63-year-old man who presented with a mobile mass in the inguinal canal consistent with an inguinal hernia. The patient was subsequently diagnosed with a liposarcoma of the spermatic cord and successfully treated with extensive local resection, including radical orchiectomy and en bloc resection of the mass and associated cord structures. No adjuvant therapy was deemed necessary, and the patient remained asymptomatic and disease-free 10 years after surgery. The details of this case are presented, along with a review and discussion of the currently available data regarding the diagnosis and management of this challenging condition.

Predictive Modeling of Massive Transfusion Requirements During Liver Transplantation and Its Potential to Reduce Utilization of Blood Bank Resources.

BACKGROUND: Patients undergoing liver transplantation frequently but inconsistently require massive blood transfusion. The ability to predict massive transfusion (MT) could reduce the impact on blood bank resources through customization of the blood order schedule. Current predictive models of MT for blood product utilization during liver transplantation are not generally applicable to individual institutions owing to variability in patient population, intraoperative management, and definitions of MT. Moreover, existing models may be limited by not incorporating cirrhosis stage or thromboelastography (TEG) parameters. METHODS: This retrospective cohort study included all patients who underwent deceased-donor liver transplantation at the Johns Hopkins Hospital between 2010 and 2014. We defined MT as intraoperative transfusion of > 10 units of packed red blood cells (pRBCs) and developed a multivariable predictive model of MT that incorporated cirrhosis stage and TEG parameters. The accuracy of the model was assessed with the goodness-of-fit test, receiver operating characteristic analysis, and bootstrap resampling. The distribution of correct patient classification was then determined as we varied the model threshold for classifying MT. Finally, the potential impact of these predictions on blood bank resources was examined. RESULTS: Two hundred three patients were included in the study. Sixty (29.6%) patients met the definition for MT and received a median (interquartile range) of 19.0 (14.0-27.0) pRBC units intraoperatively compared with 4.0 units (1.0-6.0) for those who did not satisfy the criterion for MT. The multivariable model for predicting MT included Model for End-stage Liver Disease score, whether simultaneous liver and kidney transplant was performed, cirrhosis stage, hemoglobin concentration, platelet concentration, and TEG R interval and angle. This model demonstrated good calibration (Hosmer-Lemeshow goodness-of-fit test P = .45) and good discrimination (c statistic: 0.835; 95% confidence interval, 0.781-0.888). A probability cutoff threshold of 0.25 was found to misclassify only 4 of 100 patients as unlikely to experience MT, with the majority such misclassifications within 4 units of the working definition for MT. For this threshold, a preoperative blood ordering schedule that allocated 6 units of pRBCs for those unlikely to experience MT and 15 for those who were likely to experience MT would prevent unnecessary crossmatching of 338 units/100 transplants. CONCLUSIONS: When clinical and laboratory parameters are included, a model predicting intraoperative MT in patients undergoing liver transplantation is sufficiently accurate that its predictions could guide the blood order schedule for individual patients based on institutional data, thereby reducing the impact on blood bank resources. Ongoing evaluation of model accuracy and transfusion practices is required to ensure continuing performance of the predictive model.

Outcomes and risk stratification for late antibody-mediated rejection in recipients of ABO-incompatible kidney transplants: a retrospective study.

The required intensity of monitoring for antibody-mediated rejection (AMR) after of ABO-incompatible (ABOi) kidney transplantation is not clearly formulized. We retrospectively evaluated a single-center cohort of 115 ABO-incompatible (ABOi) kidney transplant recipients, of which 32% were also HLA incompatible (ABOi/HLAi) with their donors. We used an adjusted negative binomial model to evaluate risk factors for late AMR. Using this model, we risk-stratified patients into high- and low-risk groups for the development of late AMR; 26% of patients had at least one AMR episode; 49% of AMR episodes occurred within 30-days after transplant and were considered early AMR. Patients with an early AMR episode had a 5.5-fold greater incidence of developing late AMR [IRR = 5.5, (95% CI: 1.5-19.3), P = 0.01]. ABOi/HLAi recipients trended toward increased late AMR risk [IRR = 1.9, (95% CI: 0.5-6.6), P = 0.3]. High-risk recipients (those with an early AMR or those who were ABOi/HLAi) had a sixfold increased incidence of late AMR [IRR = 6.3, (95% CI: 1.6-24.6), P = 0.008] versus low-risk recipients. The overall incidence of late AMR was 20.8% vs. 1.5% in low-risk recipients. Changes in anti-A/B titer did not correlate with late AMR (IRR = 0.9 per log titer increase, P = 0.7). This risk-stratification scheme uses information available within 30 days of ABOi transplantation to determine risk for late AMR and can help direct longitudinal follow-up for individual patients.

Three-year Results of a Pilot Program in Early Liver Transplantation for Severe Alcoholic Hepatitis.

OBJECTIVE: To examine our pilot to transplant selected patients with acute alcoholic hepatitis, initiated in October 2012. BACKGROUND: Six months of alcohol abstinence is typically required before liver transplant. A Franco-Belgian protocol showed that early transplant in severe alcoholic hepatitis could improve survival with low incidence of alcohol relapse. Application of this controversial indication is growing despite unclear generalizability. METHODS: Data was collected on all patients with alcohol-related liver disease since initiation of the pilot through June 2015. Patients were stratified into two groups: severe alcoholic hepatitis as first liver decompensation (Group 1), alcoholic cirrhosis with ≥6 months abstinence (Group 2). Alcohol relapse was defined as any evidence of alcohol consumption after transplant, which was assessed for harmful patterns of binge or frequent drinking. RESULTS: Forty-three patients underwent liver transplant, including 17 patients in Group 1. Six-month survival was 100% versus 89% for Groups 1 and 2, respectively (P = 0.27). Alcohol relapse was similar in Group 1 versus Group 2: 23.5% versus 29.2% (P > 0.99). Harmful drinking was higher in Group 1 versus Group 2, despite lack of statistical significance: 23.5% versus 11.5% (P = 0.42). CONCLUSIONS: In this pilot with carefully selected patients, early liver transplant provided excellent short-term survival, and similar rates of alcohol relapse compared with patients with 6 months of abstinence. Harmful patterns of relapse remain challenging in this population, highlighting the need for validated models to predict alcohol relapse, and need for extreme caution in selecting patients for this exceptional indication. Larger prospective studies and longer follow up are necessary.

Individual Frailty Components and Mortality in Kidney Transplant Recipients.

BACKGROUND: Frailty increases early hospital readmission and mortality risk among kidney transplantation (KT) recipients. Although frailty represents a high-risk state for this population, the correlates of frailty, the patterns of the 5 frailty components, and the risk associated with these patterns are unclear. METHODS: Six hundred sixty-three KT recipients were enrolled in a cohort study of frailty in transplantation (12/2008-8/2015). Frailty, activities of daily living (ADL)/instrumental ADL (IADL) disability, Centers for Epidemiologic Studies Depression Scale depression, education, and health-related quality of life (HRQOL) were measured. We used multinomial regression to identify frailty correlates. We identified which patterns of the 5 components were associated with mortality using adjusted Cox proportional hazards models. RESULTS: Frailty prevalence was 19.5%. Older recipients (adjusted prevalence ratio [PR], 2.22; 95% confidence interval [CI], 1.21-4.07) were more likely to be frail. The only other factors that were independently associated with frailty were IADL disability (PR, 3.22; 95% CI, 1.72-6.06), depressive symptoms (PR, 11.31; 95% CI, 4.02-31.82), less than a high school education (PR, 3.10; 95% CI, 1.30-7.36), and low HRQOL (fair/poor: PR, 3.71; 95% CI, 1.48-9.31). The most common pattern was poor grip strength, low physical activity, and slowed walk speed (19.4%). Only 2 patterns of the 5 components emerged as having an association with post-KT mortality. KT recipients with exhaustion and slowed walking speed (hazards ratio = 2.43; 95% CI, 1.17-5.03) and poor grip strength, exhaustion, and slowed walking speed (hazard ratio, 2.61; 95% CI, 1.14-5.97) were at increased mortality risk. CONCLUSIONS: Age was the only conventional factor associated with frailty among KT recipients; however, factors rarely measured as part of clinical practice, namely, HRQOL, IADL disability, and depressive symptoms, were significant correlates of frailty. Redefining the frailty phenotype may be needed to improve risk stratification for KT recipients.

Frailty, Length of Stay, and Mortality in Kidney Transplant Recipients: A National Registry and Prospective Cohort Study.

OBJECTIVE: To test whether frailty, a novel measure of physiologic reserve, is associated with longer kidney transplant (KT) length of stay (LOS), and modifies the association between LOS and mortality. BACKGROUND: Better understanding of LOS is necessary for informed consent and discharge planning. Mortality resulting from longer LOS has important regulatory implications for hospital and transplant programs. Which recipients are at risk of prolonged LOS and its effect on mortality are unclear. Frailty is a novel preoperative predictor of poor KT outcomes including delayed graft function, early hospital readmission, immunosuppression intolerance, and mortality. METHODS: We used registry-augmented hybrid methods, a novel approach to risk adjustment, to adjust for LOS risk factors from the Scientific Registry of Transplant Recipients (n = 74,859) and tested whether (1) frailty, measured immediately before KT in a novel cohort (n = 589), was associated with LOS (LOS: negative binomial regression; LOS ≥2 weeks: logistic regression) and (2) whether frailty modified the association between LOS and mortality (interaction term analysis). RESULTS: Frailty was independently associated with longer LOS [relative risk = 1.15, 95% confidence interval (CI): 1.03-1.29; P = 0.01] and LOS ≥2 weeks (odds ratio = 1.57, 95% CI: 1.06-2.33; P = 0.03) after accounting for registry-based risk factors, including delayed graft function. Frailty also attenuated the association between LOS and mortality (nonfrail hazard rate = 1.55 95% CI: 1.30-1.86; P < 0.001; frail hazard rate = 0.97, 95% CI: 0.79-1.19, P = 0.80; P for interaction = 0.001). CONCLUSIONS: Frail KT recipients are more likely to experience a longer LOS. Longer LOS among nonfrail recipients may be a marker of increased mortality risk. Frailty is a measure of physiologic reserve that may be an important clinical marker of longer surgical LOS.