Part Of Pretransplant Evaluation Research Articles

Renal Transplantation in Rare Monogenic Urinary Stone Disease – A Single-center Experience

Introduction: Monogenic urinary stone disease (MUSD) tends to be more severe with early onset of symptoms and a higher risk of chronic kidney disease than sporadic USD. The literature on the outcome after renal transplant in patients with certain MUSD is scarce. Materials and Methods: This is a retrospective single-center observational study conducted in a tertiary care renal transplant unit in North India between 2018 and 2021. The renal transplant recipients who developed an end-stage renal disease (ESRD) due to renal calculus disease/nephrocalcinosis were included in the study. All the patients presented to us in an anuric state, and hence, a 24-h urine metabolic profile could not be performed. Ear, nose, and throat and ophthalmological evaluations were done to rule out extrarenal manifestations. These patients were subjected to genetic analysis, i.e., clinical exome sequencing using next-generation sequencing. Results: Out of 283 live renal transplants, 11 patients developed ESRD due to nephrocalcinosis/renal calculus disease. Out of 11, only 4 had genetic mutations and the rest did not have any identifiable genetic mutations. The gene mutations were identified in ADCY10, CLDN16, CaSR, and SLC3A4. The patient with ADCY10 mutation had a strong family history. The clinical phenotype and in silico parameters analysis predicted the variant to be damaging except the one with CaSR mutation which causes Hypocalciuric hypercalcemia syndrome, type 1. Three of four underwent surgical intervention at younger age. All underwent successful live-related renal transplantation, with good graft function on follow-up, without any recurrence of calculus in the allograft. Conclusion: Renal transplantation can be safely proceeded in patients with the above monogenic mutations. Genetic analysis should be a part of pretransplant evaluation in young onset nephrolithiasis and end-stage kidney disease patients to look for a monogenic cause, to assess the risk of recurrence postrenal transplant.

Tuberculosis in Patients Referred for Liver Transplant: A Case Series and Review of Literature

Pre transplant evaluation of a patient provides unique opportunity to diagnose certain diseases. Tuberculosis is endemic in India and patients are often diagnosed to have tuberculosis during their pre transplant evaluation. As these patients have advanced liver disease diagnosis, treatment planning for anti-tuberculosis therapy and timing the transplant is based on individual choice. There are no established guidelines from either the west or from India. We here report 5 cases of tuberculosis diagnosed as a part of pre transplant evaluation and have summarized available knowledge on managing such patients in peritransplant period.

MO719: Contrast Nephropathy in Peritoneal Dialysis Patients: A Single-Center Experience

Abstract BACKGROUND AND AIMS Peritoneal dialysis (PD) patients are frequently exposed to contrast media through contrast-enhanced computed tomography (CT) and/or coronary angiography, which may be used as diagnostic tools or as part of pretransplant evaluation. However, the risk of contrast nephropathy frequently limits the use of these imaging techniques. The authors aim to evaluate the loss of kidney function after contrasted examination in PD patients. METHOD We performed an observational retrospective study in a population of patients with end-stage kidney disease on PD. All patients included had performed an ionized radiation-imaging exam (CT or coronary angiography), with or without contrast media. In patients who performed more than one of the aforementioned exams, only the first one was considered. Demographic and laboratory data including kidney function and dialysis dose before and after the imaging exams were collected. We divided the population into two groups (no contrast use versus contrast use) and compared them using Mann–Whitney test or Chi square. A survival analysis was performed (time to exam; outcome—loss of renal function; predictor—contrast use). RESULTS A population of 41 patients in PD, 26 in automated PD (63.4%), with a dialysis vintage of 29 (17–38) months were included in this analysis. The median time since starting PD and the exam was 15 (5–20) months, and contrast was used in 21 exams (51.2%). Five patients underwent coronary angiography and 16 were submitted to contrast-enhanced CT. Only two patients performed contrast nephropathy prophylaxis before contrast exposure. In univariate analysis, we found no difference between renal residual function, KT/v and creatinine clearance before and after the imaging exam, irrespective of contrast use. After the diagnostic exam, 19 patients lost residual renal function [median GFR 1 (1–2) mL/min/1.73 m2], and the group of patients who did not use contrast were the most affected ones; however, there was no statistical significance difference between the two groups (P = 0.08). Since we found a significant difference in the time to imaging exam between the two studied groups, we performed a survival analysis, and the use of contrast was associated with preservation of renal function (P = 0.02). A multivariate Cox analysis with age, Charlson index, GFRe pre-exam, diabetes, use of RAASi, beta-blocker, loop diuretic and spironolactone as potential confounders showed that use of contrast was not associated with loss of renal function in PD patients. CONCLUSION Our study showed that contrast nephropathy is not frequent in PD patients and that we can allow contrast media (low or iso-osmolal) as it was not associated with loss of residual renal function.

Incidence and Characteristics of Central Nervous System Involvement in Adult Acute Myeloid Leukemia Patients

Features of central nervous system (CNS) involvement in acute myeloid leukemia (AML) are not well-defined. Unlike acute lymphoblastic leukemia, there are limited guidelines for the use of intrathecal chemotherapy with induction for AML, and institutional practices vary. Unfortunately, AML patients with CNS involvement often have worse outcomes compared to those without CNS involvement (Del Principe et al., 2018; Rozovski et al., 2015). It is important to better understand the incidence and predictive clinical and features of CNS involvement in AML to identify patients for diagnostic testing and intrathecal chemotherapy. This retrospective analysis evaluated the incidence and characteristics of CNS involvement in adult AML patients at our institution.CNS screening is recommended for AML patients with specific characteristics, including CNS symptoms, monocytic phenotype, FLT3-internal tandem duplication gene mutation, and hyperleukocytosis (>100,000 white blood cells per microliter). Treatment recommendations for CNS involvement include intrathecal methotrexate, intrathecal cytarabine, or a combination of both.In this IRB-approved retrospective study, medical records were analyzed from the University of Kansas Medical Center from years 2015-2020. Patients were selected by searching the electronic medical record for adult AML patients who received a diagnostic lumbar puncture. Characteristics of interest included presence of CNS symptoms, monocytic phenotype, FLT3 mutation, and hyperleukocytosis. Characteristics that prompted CNS screening were recorded for each patient. Additional data collection included next-generation sequencing (NGS), cytogenetic results, and whether CNS screening occurred during an initial diagnosis or during an AML relapse. Lastly, the number of intrathecal chemotherapy doses was recorded for each patient.The incidence of CNS involvement was determined by dividing the number of newly diagnosed AML CNS-positive patients by the total number of newly diagnosed AML patients. Screening detection rates were determined by dividing the number of CNS-positive patients with each characteristic by the total number that received a lumbar puncture. The percentage of CNS-positive patients with each characteristic was determined by dividing the number with each specific characteristic by the total number of CNS-positive patients. The number of intrathecal chemotherapy doses required for CNS clearance was determined using data only from patients that achieved CNS clearance.Forty-eight patients met current guidelines for CNS screening; 25 were CNS-positive and 23 were CNS-negative (overall screening detection rate of 52%). The incidence of CNS involvement among all newly diagnosed adult AML patients was 3.24%. Screening detection rates were 58% for patients with 3 characteristics, 60% for 2 characteristics, 45% for CNS symptoms, and 30% for monocytic phenotype. Not enough patients presented with the FLT3 mutation or hyperleukocytosis in isolation to calculate accurate detection rates. The CNS-positive group consisted of 28% with 3 characteristics, 24% with 2 characteristics, 20% with CNS symptoms, 12% with monocytic phenotype, 4% with FLT3 mutation, 4% with hyperleukocytosis, and 36% were screened during a relapse rather than at initial diagnosis. Two patients were CNS-positive without any of our characteristics of interest (screened due to extramedullary involvement at presentation and the other was screened as part of pre-transplant evaluation). Seventeen patients achieved CNS clearance with 41% requiring 1 dose of intrathecal chemotherapy, 35% requiring 2 doses, and 24% requiring more than 2 doses. NGS and cytogenetic results did not reveal any additional associations.This data indicates that current AML CNS screening guidelines appear to properly identify a patient population at risk for CNS involvement. At our institution, 52% of screened patients were CNS-positive. This analysis also revealed a diverse distribution of characteristics among AML patients with CNS involvement, and patients commonly presented with multiple risk factors. These results emphasize the need for ongoing research to further delineate CNS involvement risk factors in AML. This data will be used for current policy analysis at our institution and potentially prospective studies to better evaluate outcomes for AML patients with CNS involvement. [Display omitted] DisclosuresLin: AbbVie, Aptevo Therapeutics, Astellas Pharma, Bio-Path Holdings, Celgene, Celyad, Genentech-Roche, Gilead Sciences, Incyte, Jazz Pharmaceuticals, Novartis, Ono Pharmaceutical, Pfizer, Prescient Therapeutics, Seattle Genetics, Tolero, Trovagene: Research Funding.

S3285 The Negative Predictive Value of Dobutamine Stress Echocardiography for Identifying Coronary Artery Disease in Liver Transplant Evaluation

INTRODUCTION: Coronary artery disease (CAD) is associated with increased morbidity and mortality in end-stage liver disease (ESLD) patients undergoing liver transplant(LT). Dobutamine stress echocardiography (DSE) has gained preference over other screening tests for detecting CAD in ESLD patients due to the chronic systemic vasodilatation, increased cardiac output, and poor exercise tolerance. This study aimed to evaluate the negative predictive value and the accuracy of DSE for the diagnosis of obstructive CAD, using coronary angiography as the reference in ESLD patients. METHODS: This is a retrospective single-center study at Methodist University Hospital, Memphis TN, which included patients with ESLD undergoing LT evaluation. We reviewed patients from three consecutive years and identified the patients who underwent DSE as part of pre-transplant evaluation along with coronary angiography within six months of DSE. A total of 94 patients were identified that had both a DSE along with coronary angiography for LT evaluation. Beta-blockers were held prior to DSE, and the target heart rate for DSE was 85% age-predicted maximum heart rate. Of the 94 patients, nine patients did not achieve a maximal heart rate despite maximal medication. An analysis was performed with the remaining 85 patients. Patients were referred for coronary angiography if DSE was abnormal or with a normal DSE in the presence of ≥1 risk factor(s) for CAD. Significant CAD was defined as ≥70% obstruction or fractional flow reserve < 0.80. RESULTS: A total of 22 patients had a DSE positive test and were referred to coronary angiography: 5/22(23%) patients had positive coronary angiography and 18/22(82%) had negative coronary angiography. The sensitivity in this group was 63% and specificity of 78%. Interestingly, 63 patients were referred for coronary angiography with a negative DSE due to CAD risk factors: 3/63(5%) patients had a positive coronary angiography, and 60/63(95%) patients had a negative coronary angiography. The negative predictive value of DSE at detecting obstructive CAD in ESLD patients is 95% (Table 1). The accuracy of DSE at detecting obstructive CAD in ESLD patients is 76%. CONCLUSION: Due to the hemodynamics of the ESLD patients, the sensitivity of DSE is limited. However, the negative predictive value is high (95%) to use DSE as a cost-effective, non-invasive screening test to rule out CAD.Table 1

Not so innocent bystander - gallbladder varices without portal vein thrombosis

Introduction. Gallbladder varices (GBV) represent a rare form of ectopic varices that usually occur in patients with portal hypertension and portal vein thrombosis. Case outline. We present a case of a 38-year-old woman with decompensated autoimmune liver cirrhosis who was referred to our institution for evaluation for liver transplantation. She was incidentally discovered to have GBV during a routine B-mode abdominal ultrasonography as part of pre-transplant evaluation. GBV were confirmed by the Color Doppler Sonography, and multi detector computed tomography angiography. Interestingly, portal vein was patent and without thrombus. Conclusion. Despite being asymptomatic in most cases, the presence of GBV is valuable information for a surgeon because they might be a source of potentially catastrophic bleeding, which is particularly poorly tolerated by patients with decompensated liver cirrhosis. Ultrasound has the irreplaceable role not only in discovering GBV, but in prompt diagnosis of rare, but unpredictable and fatal complications as well.

Core Muscle Size Predicts Postoperative Outcome in Lung Transplant Candidates

Careful patient selection is the prerequisite to raise transplant benefit. In lung transplant (LT) candidates, the effect of body mass index (BMI) on postoperative outcome remains controversial, possibly due to the inaccuracy of BMI in discriminating between fat and muscle mass. We therefore hypothesized that assessment of body composition by muscle mass measures is more accurate than by BMI regarding postoperative outcome. All LT recipients from 2011 to 2014 were included and retrospectively analyzed. Lean psoas area (LPA) was assessed from pretransplant computed tomography scans, and associations with postoperative outcomes were investigated. Included were 103 consecutive LT recipients with a mean pre-LT BMI of 22.0 ± 4.0 kg/m(2) and a mean LPA of 22.3 ± 8.3 cm(2). LPA was inversely associated with length of mechanical ventilation (p = 0.03), requirement of tracheostomy (p = 0.035), and length of stay in the intensive care unit (p = 0.02), while controlling for underlying disease, BMI, sex, age, and procedure; in contrast, BMI was not (p = 0.25, p = 0.54, and p = 0.42, respectively.). Multiple regression analysis revealed that the 6-minute walk distance at the end of pulmonary rehabilitation was significantly associated with LPA (p = 0.02). LPA can easily be assessed in LT candidates as part of pretransplant evaluation and was significantly associated with short-term outcome, whereas BMI was not. Assessment of LPA may provide additional information on body composition beyond BMI. However, the clinical utility has to be further evaluated.

Central Nervous System Involvement in Acute Myeloid Leukemia Patients Undergoing Hematopoietic Cell Transplantation

Central nervous system (CNS) involvement is considered rare in adults with acute myeloid leukemia (AML). Therefore the cerebrospinal fluid (CSF) is typically examined only in patients with CNS symptoms. In our institution all AML patients considered candidates for allogeneic hematopoietic cell transplantation (HCT) undergo routine CSF examination as part of pre-transplant evaluation, allowing a relatively unbiased look at the incidence of AML in CSF pre-HCT. The primary objectives of this study were to assess the rate of CNS involvement in AML patients undergoing HCT, evaluate potential risk factors for CNS disease, and examine the effect of CNS involvement on transplant outcome.We retrospectively evaluated 327 adults with AML who underwent ablative HCT between January 2007 and December 2012. Median age was 49 (range 19-73). Twenty eight (8%) patients had favorable karyotype, 215 (66%) had intermediate-risk karyotype, and 84 (26%) had unfavorable karyotype at diagnosis. 206 patients had received a high intensity induction regimen (daily ARA-C dose ≥ 500mg/m2). At time of CSF evaluation pre-HCT, 166 patients were in CR without minimal residual disease (MRD), 65 had CR with MRD, 41 had CRp or CRi, and 54 were in relapse. Median follow-up time was 630 days.22 patients (7%) had CSF AML involvement, as assessed morphologically or using multiparameter flow cytometry, at their pre-HCT evaluation. 5 of these patients had had prior (treated) CNS AML, 3 had had prior extramedullary disease (EMD) not involving the CNS, and 2 had had both prior CNS and other extramedullary disease (Fig. 1). The incidence of CSF AML at pre-HCT evaluation was 7/20 in patients with past CNS involvement vs. 15/ 307 in patients without history of CNS disease (p <0.001), and was 5/30 in patients with a history of other EMD vs. 17/297 in patients without a history of EMD (p = 0.04). Other covariates associated with CNS AML at pre-HCT evaluation were higher WBC at diagnosis (p <0.001, medians of 34,000 in those with and 5,000 in those without CNS disease) and disease status (p<0.001) with only 2% of patients in CR without MRD had CSF involvement vs. 8% of those with CR with MRD, 7% of those with CRp or CRi, and 19% of those with relapse disease at time of pre-HCT evaluation. Cytogenetics, age, karyotype, and receipt of HiDAC showed no effect on CSF involvement pre-HCT in a univarate analysis.Classification and regression tree (CART) analysis identified 3 risk groups: (1) high = prior CNS disease (20 pts, 35% with CSF involvement at pre-HCT evaluation), (2) intermediate = no prior CNS involvement but in systemic relapse at pre-HCT CSF evaluation (51 pts, 16% with CSF involvement at pre-HCT evaluation), (3) low = no prior CNS disease and either CR (+/- MRD) or CRp/CRi (254 pts, 3% with CSF involvement at pre-HCT evaluation).All 22 patients with CSF involvement at pre-HCT evaluation received CNS-directed treatment (intrathecal chemotherapy +/- intracranial irradiation) and cleared their CNS disease prior to transplant. 18 patients also received CNS-directed therapy after HCT (between 1-6 intrathecal treatments). Nine and 8 patients with prior history of CNS disease, but with no evidence of CSF involvement at time of pre-HCT evaluation, received CNS-directed therapy before and after transplant respectively. Two of 35 patients (6%) with CNS disease at any time pre-HCT had documented CNS disease after transplant.While patients with CSF involvement at pre-HCT evaluation had shorter post-HCT survival (p = 0.002) (Fig. 2), multivariate analysis indicated that this reflected the association of CNS disease with poorer systemic response to therapy and evidence of systemic disease at time of transplant; specifically multivariate hazard rates were 1.48 for CNS involvement vs no CNS involvement (p = 0.17), contrasted with 3.62 for CR with MRD vs CR without MRD (p <0.001) and 3.78 for no CR vs CR without MRD (p <0.001). Tests for interactions indicated that the relatively small effect of CNS disease on survival was similar in patients with CR (+/- MRD), CRp or CRi, or relapse disease at time of CSF evaluation pre-HCT.We conclude that CNS AML involvement pre-HCT is relatively uncommon (7%), is primarily associated with a history of prior CNS disease, and, when controlled, is not an independent factor in determining survival after HCT. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

All Patients with Chronic Hepatitis C Over the Age of 50 Should Have Screening Colonoscopy Prior to Interferon Therapy

All Patients with Chronic Hepatitis C Over the Age of 50 Should Have Screening Colonoscopy Prior to Interferon Therapy Ramesh Koka, Gaurav Mehta, Victor Araya, Kenneth D. Rothstein Background: The prevalence of polyps on screening colonoscopy has been well studied in patients with cirrhosis and as part of pre-transplant evaluation. Recent studies have indicated that there might be an increased prevalence in cirrhotics especially in the age group ! 50 with prevalence rates of up to 40%. There have been no studies examining the prevalence of polyps or colorectal cancer specifically in patients with chronic hepatitis C. Aim: Our goal was to examine the prevalence of polyps in patients with chronic hepatitis C to determine if there was an increase compared to the average risk population. Methods: Retrospective database review identified 181 screening colonoscopies performed in patients with chronic hepatitis C between 1998 & 2004. Histological data on the polyps removed were also examined. Results: 181 screening colonoscopies were performed, 42 were excluded for repeat colonoscopy, rectal bleeding, or prior history of polyps. Of the 139 analyzed, 86 were men & 53 were women. 56/139 (40%) had polyps of which 24/139 (17%) had tubular adenomas. Other pathologies noted at colonoscopy included diverticulosis, AVMs and hemorrhoids. No cancers or dysplasia was recorded in this group of patients. Men had 17/86 (19.7%) had tubular adenomas compared to women 7/53(13%). When subdivided by race, Caucasians (W) had higher rates of tubular adenomas 9/43(21%) compared to African Americans (AA) 12/82 (14.6%). Conclusions: The prevalence of polyps in patients with chronic hepatitis C in our study is comparable to that of the asymptomatic average risk population (24-47%) though the mean age was lower than in prior studies (56 compared to 62.5). Since the incidence of polyps increases with advancing age, this study suggests that patients with chronic hepatitis C may have a higher prevalence of colonic polyps. All patients with chronic hepatitis C over the age of 50 should be screened with colonoscopy prior to treatment given the significant prevalence of colon polyps, especially tubular adenomas. Abstracts