Prevalence, Risk Factors, Treatment, and Overall Impact of BK Viremia on Kidney Transplantation.

BK viremia (BKV) is a recognized and potentially serious problem in renal transplantation. The risk factors and the impact of BKV on renal allograft and patient survival are controversial. This study reports an 8-year, single-center experience on the prevalence, risk factors, and outcomes of BKV in kidney transplant recipients. This is a retrospective analysis of all patients who received a kidney transplant at the University of Kentucky and had BK viral titers available from 2009 to 2017. BKV was defined by a polymerase chain reaction viral load of ≥ 10,000 copies per mL. Demographic, clinical, and laboratory data generated during routine outpatient follow up and inpatients records were collected. Independent risk factors for BKV were determined using uni- and multivariate analysis. Graft and patient survival was compared using Kaplan-Meier analysis, and the severity of polyomavirus nephropathy on biopsy was scored using the Banff 2017 classification. We identified 122 BK positive (19%) and 527 BK negative (81%) patients. BKV developed after a median of 115 days (range, 80-249 days) following kidney transplantation. The 1-, 5-, and 10-year graft survival was 97%, 75%, and 33% in the BKV group and 96%, 85%, and 71% in the BK negative group, respectively. Likewise, the 1-, 5-, and 10-year patient survival was 98%, 84%, and 52% in the BKV group and 98%, 92%, and 84% in the BK negative group. Male sex, age at transplantation, maintenance steroids, and alemtuzumab induction were associated with developing BKV in the multivariate analysis. We concluded that BKV is not uncommon after renal transplantation. The determinants for BKV are male sex, older transplant recipients, and maintenance steroids. BKV adversely affected graft and patient survival. A unified approach for BKV and polyomavirus nephropathy treatment is needed.

Association Between Sarcopenia and AFP Level in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: Sarcopenia is one of the most common complications of cirrhosis. Liver transplantation (LT) is the treatment of choice for patients with early-stage hepatocellular carcinoma (HCC) that are unsuitable for resection. METHODS: We performed a retrospective analysis of 163 patients transplanted at our institution with HCC from 1998 to 2016. Sarcopenia was diagnosed based on the skeletal muscle mass on computed tomography imaging using SliceOmatic 5.0 software at L3 level (≤52.4 cm2/m2 in males and ≤38.5 cm2/m2 in females). RESULTS: From the 163 patients who underwent LT for HCC, 119 had available computed tomography scan. From those, 61 were identified as sarcopenic by lumbar skeletal muscle index (LSMI), of which 53 patients were male (86.9%) with a median age of 59 y (56-64). The most common etiologies of cirrhosis were hepatitis C virus infection (55.7%) and alcohol liver disease (46.7%). A multivariable analysis was performed to find predictors of sarcopenia. Alpha-fetoprotein level >100 mg/dL (OR, 6.577; 95% CI: 1.370-51.464; P = 0.034) and gender (male) (OR, 5.878; 95% CI: 1.987-20.054; P = 0.002) were independently associated with the presence of sarcopenia in this cohort. Patients in the lowest quartile for LSMI had prolonged length of stay compared to the rest of the patients (P = 0.029). CONCLUSIONS: Alpha-fetoprotein level >100 mg/dL is associated with almost 6-fold increased risk of sarcopenia in patients with HCC undergoing LT. Patients in the lowest quartile of the LSMI are associated with 70% increased risk of prolonged length of stay in this cohort.

Outcome of Patients With Small Vessel Vasculitis After Renal Transplantation: National Database Analysis.

BACKGROUND: Small vessel vasculitis commonly affects the kidney and can progress to end-stage renal disease. The goal of this study is to compare outcomes of patients who received a renal transplant as a result of small vessel vasculitis (group A) with those who received kidney transplants because of other causes (group B). METHODS: This is a retrospective analysis of United Network for Organ Sharing registry data for adult primary kidney transplants from January 2000 to December 2014. Group A patients (N = 2196) were compared with a group B (N = 6588); groups were case matched for age, race, sex, donor type, and year of transplant in a 1:3 ratio. RESULTS: Renal and patient survivals were better in the group A (P < 0.001). New-onset diabetes after transplant developed in 8.3% of the group A and 11.3% of group B (P < 0.001). Seventeen (0.8%) patients in group A developed recurrent disease. Of these, 7 patients had graft failure, 3 of which were due to disease recurrence. Group A patients had significantly higher risk of developing posttransplant solid organ malignancies (11.3% vs 9.3%, P = 0.006) and lymphoproliferative disorder (1.3% vs 0.8%, P = 0.026). Independent predictors of graft failure and patient mortality were recipients' morbid obesity, diabetes, age, and dialysis duration (hazard ratio of 1.7, 1.4, 1.1/10 years, and 1.1/year for graft failure, and 1.7, 1.7, 1.6/10 years and 1.1/year for patient mortality, respectively). CONCLUSIONS: Renal transplantation in patients with has favorable long-term graft and patient outcomes with a low disease recurrence rate. However, they may have a higher risk of developing posttransplant malignancies.

Kidney Transplant Outcomes in the Super Obese: A National Study From the UNOS Dataset.

BACKGROUND: We evaluated outcomes of super-obese patients (BMI > 50) undergoing kidney transplantation in the US. METHODS: We performed a review of 190 super-obese patients undergoing kidney transplantation from 1988 through 2013 using the UNOS dataset. RESULTS: Super-obese patients had a mean age of 45.7 years (21-75 years) and 111 (58.4 %) were female. The mean BMI of the super-obese group was 56 (range 50.0-74.2). A subgroup analysis demonstrated that patients with BMI > 50 had worse survival compared to any other BMI class. The 30-day perioperative mortality and length of stay was 3.7 % and 10.09 days compared to 0.8 % and 7.34 days in nonsuper-obese group. On multivariable analysis, BMI > 50 was an independent predictor of 30-day mortality, with a 4.6-fold increased risk of perioperative death. BMI > 50 increased the risk of delayed graft function and the length of stay by twofold. The multivariable analysis of survival showed a 78 % increased risk of death in this group. Overall patient survival for super-obese transplant recipients at 1, 3, and 5 years was 88, 82, and 76 %, compared to 96, 91, 86 % on patients transplanted with BMI < 50. A propensity score adjusted analysis further demonstrates significant worse survival rates in super-obese patients undergoing kidney transplantation. CONCLUSION: Super-obese patients had prolonged LOS and worse DGF rates. Perioperative mortality was increased 4.6-fold compared to patients with BMI < 50. In a subgroup analysis, super-obese patients who underwent kidney transplantation had significantly worse graft and patient survival compared to underweight, normal weight, and obesity class I, II, and III (BMI 40-50) patients.

Cancer stem cell marker expression alone and in combination with microvascular invasion predicts poor prognosis in patients undergoing transplantation for hepatocellular carcinoma.

BACKGROUND: The cancer stem cell hypothesis provides an explanation for hepatocellular carcinoma (HCC) heterogeneity. We investigated the expression of CD44 and CD133 alone and in combination with microvascular invasion (MVI) as predictors of prognosis in patients undergoing liver transplantation for HCC. METHODS: Explanted livers from 95 patients transplanted for HCC were analyzed. Marker expression was evaluated by immunofluorescence. RESULTS: Seventy-seven patients were male with a mean age of 56 years. The most common etiologies of cirrhosis were hepatitis C (50%) and alcoholic liver disease (41%). Forty-one patients had laboratory model for end-stage liver disease score greater than 15. Overall survival (OS) at 1-, 3-, and 5-years was 86%, 75%, and 64%, respectively. Recurrence rate was 13% with a median follow-up of 64 months. The 5-year OS was significantly lower in those patients with MVI and CD44 (36.9%) or CD133 (40%). CD44(+) and CD133(+) correlated with increased risk of poorly differentiated HCC, and elevated alpha-fetoprotein levels. In combination with MVI, both markers were independently associated with increased recurrence and worse OS (recurrence P < .003, odds ratio = 8.05; P = .001, odds ratio = 9.5, survival P = .001, HR = 3.7; P = .004, HR = 3.2 respectively). CONCLUSIONS: CD44 or CD133 alone and in combination with MVI are independent predictors of poor prognosis in patients undergoing transplantation for HCC.

Nonalcoholic steatohepatitis is strongly associated with sarcopenic obesity in patients with cirrhosis undergoing liver transplant evaluation.

BACKGROUND: Sarcopenia is the most common complication of cirrhosis and adversely affects quality of life and outcomes before, during, and after liver transplantation. We studied predictors of sarcopenia and sarcopenic obesity in patients with cirrhosis undergoing liver transplant (LT) evaluation. METHODS: A retrospective analysis of 207 adult cirrhotic patients that underwent LT from January 2008 to December 2013 was performed at our institution. RESULTS: Two hundred seven patients were evaluated, 68% were male with a mean age of 54 ± 8 years. The most common etiology of cirrhosis was alcoholic liver disease (38.6%), followed by chronic hepatitis C (38.2%), nonalcoholic steatohepatitis (NASH) (21.7%), and hepatocellular carcinoma (HCC) (24.6%). The mean body mass index of the cohort was of 30.1 ± 5.7 kg/m(2) . Forty-eight percent of these patients were obese. Of the 207 patients, 88% had computed tomographic (CT) scans within 90 days before transplant; of these, 59% had sarcopenia found during LT evaluation. Of the patients with pretransplant sarcopenia, 59 had CT scan at 6 months posttransplant and 56 (95%) remained sarcopenic. Of the 56 patients who had sarcopenia at 6 months, 31 had available CT scans at 1 year, and 100% persisted with sarcopenia. These 31 subjects had a mean skeletal muscle index of 35 at 6 months and 36 at 1 year. SO was found in 41.7% of our patients. On multivariable regression analysis, obesity and age were found to be independently associated with pretransplant sarcopenia after controlling for gender and alcohol liver disease diagnosis (P = 0.00001, odds ratio [OR] 0.22, and P = 0.008, OR 2.0, respectively). A multivariable logistic regression analysis found that NASH as cause of cirrhosis and model of end-stage liver disease score are independent predictors of sarcopenic obesity after controlling for age, gender, alcoholic liver disease diagnosis, and HCC (P = 0.014 and 0.038, respectively; 95% confidence interval, 1.44-25.26 and 1.00-1.15, respectively; OR 6.03, 1.08, respectively). CONCLUSIONS: Sarcopenia and sarcopenic obesity is seen in a significant number of patients with cirrhosis undergoing LT evaluation. Sarcopenia progresses after LT initially and does not recover at least within the first year after surgery. Obesity is an independent predictor of pretransplant sarcopenia and NASH was associated with 6-fold increased risk of having sarcopenic obesity in cirrhotic patients in our cohort.