Faculty Bibliography

Background: Many uremic retention solutes are products of gut bacterial metabolism. Protein-binding renders these solutes poorly dialyzable. In a prior study we observed that a single dose of 250 mg of vancomycin, given by mouth, resulted in a significant (40%) decrease in the plasma concentration of indoxyl sulfate and p-cresyl sulfate over a period of one week. In this study we compared the changes in plasma concentration of a panel of protein-bound uremic retention solutes in response to the once-weekly oral administration of 250 mg of vancomycin or placebo over a period of 8 weeks.
Method(s): Eight subjects with chronic, stable ESRD on thrice-weekly hemodialysis via AV fistula in the River Renal Dialysis Unit in Bellevue Hospital, were randomized to two groups, utilizing a single-blinded procedure. Baseline plasma samples were collected prior to the initial dose of vancomycin or placebo and at weeks one, two, three, four, and eight. Uremic retention solutes were measured by MS-HPLC.
Result(s): Six of the eight uremic retention solutes (Table 1) demonstrated a significant decline in concentration over the eight week period of once-weekly vancomycin administration. The magnitude of the decline makes it more likely that gut production was reduced rather than renal excretion increased. Solute concentrations remained unchanged over the same period of placebo administration.
Conclusion(s): The significant decline in the plasma concentrations of multiple uremic retention solutes provides evidence of the importance of the gut microbiome in the generation of these solutes. The reduction in concentrations of indoxyl sulfate, p-cresyl sulfate, and kynurenic acid, recognized as likely uremic toxins, suggests that altering the gut microbiome might provide a valuable therapeutic strategy in the management of ESRD

OBJECTIVES/SPECIFIC AIMS: Determine timing of risk of readmissions within 30 days among patients first discharged to a skilled nursing facilities (SNF) after heart failure hospitalization and subsequently discharged home. METHODS/STUDY POPULATION: This was a retrospective cohort study of patients with SNF stays of 30 days or less following discharge from a heart failure hospitalization. Patients were followed for 30 days following discharge from SNF. We categorized patients based on SNF length of stay (LOS): 1-6 days, 7-13 days, 14-30 days. We then fit a piecewise exponential Bayesian model with the outcome as time to readmission after discharge from SNF for each group. Our event of interest was unplanned readmission; death and planned readmissions were considered as competing risks. Our model examined 2 different time intervals following discharge from SNF: 0-3 days post SNF discharge and 4-30 days post SNF discharge. We reported the hazard rate (credible interval) of readmission for each time interval. We examined all Medicare fee-for-service (FFS) patients 65 and older admitted from July 2012 to June 2015 with a principal discharge diagnosis of HF, based on methods adopted by the Centers for Medicare and Medicaid Services (CMS) for hospital quality measurement. RESULTS/ANTICIPATED RESULTS: Our study included 67,585 HF hospitalizations discharged to SNF and subsequently discharged home [median age, 84 years (IQR; 78-89); female, 61.0%]; 13,257 (19.2%) were discharged with home care, 54,328 (80.4%) without. Median length of SNF admission was 17 days (IQR; 11-22). In total, 16,333 (24.2%) SNF discharges to home were readmitted within 30 days of SNF discharge; median time to readmission was 9 days (IQR; 3-18). The hazard rate of readmission for each group was significantly increased on days 0-3 after discharge from SNF compared with days 4-30 after discharge from SNF. In addition, the hazard rate of readmission during the first 0-3 days after discharge from SNF decreased as the LOS in SNF increased. DISCUSSION/SIGNIFICANCE OF IMPACT: The hazard rate of readmission after SNF discharge following heart failure hospitalization is highest during the first 6 days home. Length of stay at SNF also has an effect on risk of readmission immediately after discharge from SNF; patients with a longer length of stay in SNF were less likely to be readmitted in the first 3 days after discharge from SNF.

Learning Objective #1: Recognize that PTLD as part of the differential when post transplant individuals present with unexplained pain, fever, or organ dysfunction. Learning Objective #2: Burkitt Lymphoma subtype as well as CNS involvement represent more aggressive manifestations of PTLD and should be managed more aggressively. CASE: 72 year-old man with end stage renal disease secondary to diabetic nephropathy status post living donor renal transplant on tacro-limus presents with headache, diplopia, and blurry vision found to have CNIII palsy on neurologic examination. Facial CT and Gadolinium enhanced Brain MRI showed complete bilateral maxillary sinus opacification and leptomeningeal enhancement. He was started on broad spectrum antibiotics, but given continuous headache and concern for meningitis a lumbar puncture was performed. CSF studies showed atypical lymphocytes of predominantly monoclonal B cells. CSF FISH showed rearrangement of c-myc oncogene negative for rearrangement of bcl6 or bcl2. Serum LDH was elevated and peripheral EBV PCR was positive. Bone marrow biopsy was negative for malignancy. Further CT imaging revealed thickening of the small bowel and mesenteric lymph-adenopathy. Patient was started on dexamethasone, intrathecal metho-trexate, and R-Hyper CVAD with interval regression of abdominal LAD, mass, improvement in ptosis, and decrease in LDH. IMPACT: The case represents an uncommon manifestation of an rare variant of disease that should warrant a different approach to diagnosis and treatment. DISCUSSION: PTLD is a well recognized, heterogenous group of disorders. The mechanism of PTLD involves EBV-induced B cell proliferation and antigen mediated T cell activation which upregulate pro-growth factors such as c-Myc. The result of which ranges from early mononucleosis-like illness, polyclonal lymphoid infiltrates, to lymphomas. Therapy involves immune reconstitution, local surgical excision, corticosteroids, antiviral agents, radiation and chemotherapy. Burkitt Lymphoma (BL) is a distinct form of PTLD. BL is an aggressive, mature B cell lymphoma composed of a monomorphic population of lymphoid cells with high mitotic and proliferation rates. Monoclonality is shown as isolated c-myc rearrangement as opposed to rear-rangements in c-myc, bcl6, and bcl2 seen in diffuse large B cell lymphoma, the most common form of PTLD. BL represents a distinct monomorphic PTLD and should be managed more aggressively with lymphoma specific chemotherapy rather than simply decreasing immunosuppression. CNS involvement of PTLD is rare, reportedly in 7-15% of all PTLD, when present is predictive of inferior survival. Compared to non-PCNS PTLD, primary CNS PTLD has a higher incidence of monomorphic EBV related disease, and late involvement with poor survival. Prior kidney transplant were also more frequent in primary CNS PTLD compared to other forms of PTLD. As a parallel, in systemic non hodgkins lymphoma, renal localization is also associated with high rates of CNS involvement