Benefit of B7-1 staining and abatacept for treatment-resistant post-transplant focal segmental glomerulosclerosis in a predominantly pediatric cohort: time for a reappraisal.

BACKGROUND: Primary FSGS manifests with nephrotic syndrome and may recur following KT. Failure to respond to conventional therapy after recurrence results in poor outcomes. Evaluation of podocyte B7-1 expression and treatment with abatacept (a B7-1 antagonist) has shown promise but remains controversial. METHODS: From 2012 to 2020, twelve patients developed post-KT FSGS with nephrotic range proteinuria, failed conventional therapy, and were treated with abatacept. Nine/twelve (< 21 years old) experienced recurrent FSGS; three adults developed de novo FSGS, occurring from immediately, up to 8 years after KT. KT biopsies were stained for B7-1. RESULTS: Nine KTRs (75%) responded to abatacept. Seven of nine KTRs were B7-1 positive and responded with improvement/resolution of proteinuria. Two patients with rFSGS without biopsies resolved proteinuria after abatacept. Pre-treatment UPCR was 27.0 ± 20.4 (median 13, range 8-56); follow-up UPCR was 0.8 ± 1.3 (median 0.2, range 0.07-3.9, p < 0.004). Two patients who were B7-1 negative on multiple KT biopsies did not respond to abatacept and lost graft function. One patient developed proteinuria while receiving belatacept, stained B7-1 positive, but did not respond to abatacept. CONCLUSIONS: Podocyte B7-1 staining in biopsies of KTRs with post-transplant FSGS identifies a subset of patients who may benefit from abatacept. A higher resolution version of the Graphical abstract is available as Supplementary information.

The role of preemptive antimicrobial therapy in kidney recipients of urine-only positive donor cultures.

BACKGROUND: The use of preemptive antimicrobial therapy for recipients of donors with microbial growth on pre-transplant urine cultures remains poorly studied. METHODS: Single-center retrospective study of kidney transplant recipients of allografts from deceased donors with urine-only (ie, in absence of donor bacteremia) positive cultures (September 2011 to August 2015). Transplant outcomes, including donor-derived infections (DDI) within the first three months post transplant, were analyzed. RESULTS: Of the 970 kidney transplants performed during the study period, urine cultures were obtained from all donors, and of these, 27 (2.8%) yielded growth. Twenty-nine (73%) recipients were treated preemptively after transplantation. All of the recipients of donors with urine cultures positive for Enterococcus, Pseudomonas, or Candida spp. received therapy whereas only one of seven recipients with urine cultures positive for Escherichia coli was treated (P < .0001). All E coli isolates were susceptible to trimethoprim-sulfamethoxazole (TMP-SMX), which was given to all patients for Pneumocystis pneumonia (PCP) prophylaxis. Infection within 3 months was evident in 16 (40%) patients: 10 out of 29 (35%) in the preemptive group and 6 out of 11 (55%) in the not-treatment group (P = .29). Evidence of DDI occurred in two recipients, one in each group. There were no differences in one-year graft and patient survival between groups. CONCLUSION: Preemptive antibiotic therapy did not seem to impact transmission events and transplant outcomes in this small cohort. Low transmission rates might have been influenced by administration of PCP prophylaxis and universal preemptive therapy for positive donor urine cultures with virulent organisms. Larger studies are needed.

Highly Sensitized Patients: Miami Transplant Institute Experience.

BACKGROUND: Transplantation continues to be challenging in highly sensitized patients. Herein, we compared induction immunosuppression (IS) based on immunologic risk stratification and desensitization with intravenous immunoglobulin (IVIG). METHODS: Of the 42 highly sensitized kidney and 3 kidney-pancreas transplant recipients who underwent IVIG for desensitization from 2008-2014, 10 (Control group) received standard induction IS with antithymocyte globulin, basiliximab, and methylprednisolone, and 35 (Rituximab group) received standard IS with rituximab ± IVIG ± plasmapheresis. Immunologic risk stratification was based on donor specific antibodies (DSA), flow crossmatch ratio, and calculated panel reactive antibody. All patients received tacrolimus, mycophenolate, and steroids for maintenance IS. Unacceptable antigen cut-offs for class I and II DSA were 6000 and 9000 mean fluorescence intensity and 2.0 and 4.4 channel shift ratios for T and B cell flow cytometry crossmatch, respectively. All complement dependent cytotoxicity T cell crossmatch negative patients were transplanted. RESULTS: Characteristics between groups, including high risk level, previous transplantation rate, number of human leukocyte antigen mismatches, delayed graft function rate, rejection rate, serum creatinine, and estimated glomerular filtration rate at 1 year (1.48 ± 0.6 and 50 ± 17 versus 1.1 ± 0.4 mg/dl and 66 25 ml/min) were not statistically significant between the Control and the Rituximab groups, respectively. Waiting time for the Control group was 6.4 years versus 4.1 years for the Rituximab group (p = 0.009). The cumulative proportion of patients who remain free of death or allograft failure was significantly higher in the Rituximab (87%) versus the Control group (60%) (p = 0.047). CONCLUSIONS: In highly sensitized patients who received desensitization with IVIG, the addition of Rituximab to our standard IS (and/or IVIG and plasmapheresis as per the immunologic risk stratification model) resulted in higher cumulative patient and graft survival.

Economic impact of ambulatory care formulary restrictions at a large county health system.

PURPOSE: Study results documenting substantial cost savings achieved by an outpatient indigent-care pharmacy program through formulary modifications and optimized purchasing practices are presented. METHODS: Wholesale purchasing data were retrospectively evaluated to compare drug expenditures before and after a large Florida hospital's adoption of a tiered formulary system for three ambulatory care facilities serving mostly uninsured patients. The outcomes assessed included the average cost per prescription and total medication purchases before and after implementation of the tiered formulary, which was phased in over several months and accompanied by intensive educational programs targeting physicians and pharmacy staff. Other outcomes included cost avoidance resulting from an increased emphasis on patient assistance program (PAP) enrollment and the use of "bulk replacement" arrangements for prescription replenishment. RESULTS: During a designated nine-month postimplementation period, the average cost per prescription declined by 4.7% (from $19.86 to $18.92) relative to the baseline value. Six-month spending decreases of 36-58% from prior-year levels were achieved in 7 of the 10 most-purchased drug classes, with an overall 25% decline in medication purchases. Cost avoidance due to more aggressive use of PAPs and bulk replacement programs also yielded substantial program savings. CONCLUSION: Formulary streamlining and other cost-control initiatives at an outpatient pharmacy program were associated with a decrease in the average cost per prescription of $0.94 over a nine-month period. The primary endpoint showed a potential annualized savings of approximately $1 million.