Late Conversion to Belatacept After Kidney Transplantation: Outcome and Prognostic Factors.

BACKGROUND: Conversion to belatacept at a later point after kidney transplantation (KT) as a rescue therapy has been shown to be beneficiary in an increasing number of patients, but prognostic factors for a favorable outcome have never been investigated. METHODS: The present study analyzed all KT patients after late conversion to belatacept in a single center regarding graft survival and changes in estimated glomerular filtration rate (eGFR), proteinuria, and mean fluorescence intensity (MFI) of donor-specific antibodies (DSA). RESULTS: A total of 69 KT patients were converted to belatacept. eGFR increased from 28.9 ± 18.2 mL/min/1.73 m2 at time of conversion to 34.8 ± 20.1 mL/min/1.73 m2 after 18 months (P = .025). After conversion, 26/69 patients (37.7%) showed a sustained increase in eGFR of >5 mL/min/1.73 m2 after 12 months and were defined as responders. All other patients (43/69, 62.3%) were defined as nonresponders. In multivariate analysis, nonresponders presented with significantly higher proteinuria (552 ± 690 vs 165 ± 158 mg/L; P = .004) at the time of conversion. Changes of eGFR from before conversion and the time of conversion were similar in both subgroups (-5.7 ± 9.2 and 29.2 ± 17.3 mL/min/1.73 m2 in responders and -4.6 ± 10.7 and 28.7 ± 19.0 mL/min/1.73 m2 in nonresponders). HLA antibody panel reactivity did not change after conversion. DSA-MFI was higher in nonresponders (7,155 ± 6,785) than in responders (2,336 ± 2,173; P = .001). One patient (1/69, 1.4%) developed de novo DSA after conversion, and no antibody-mediated rejection was diagnosed within 1,540 treatment months. CONCLUSIONS: Late conversion to belatacept is beneficiary for a subgroup of patients, with lower proteinuria at the time of conversion being an indicator for a favorable outcome.

Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae-Related Urinary Tract Infection in Kidney Transplant Recipients: Risk Factors, Treatment, and Long-Term Outcome.

BACKGROUND: Prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) has risen in kidney transplant (KT) patients, with no long-term data so far on graft function or survival. METHODS: KT patients with ESBL-E-positive urine culture were retrospectively analyzed regarding initial adequate antimicrobial therapy, recurrent infection, transplant function, and survival compared with an ESBL-E-negative KT control cohort. RESULTS: ESBL-E-positive KT patients (n = 93) were older (55.5 ± 16.1 vs 49.5 ± 16.8 y; P = .001), presented with higher trough levels of cyclosporine and tacrolimus (121 ± 71 vs 102 ± 32 ng/mL [P = .04]; and 7.9 ± 3.3 vs 7.0 ± 2.3 ng/mL [P = .04], respectively), higher dosages of mycophenolate (1,533 ± 670 vs 1,493 ± 436; P = .001), and more acute rejection episodes within 3 months before diagnosis (12.9% vs 0.8%; P < .0001) compared with control subjects (n = 591). Five-year patient survival was superior in control subjects compared with ESBL-E-positive patients (91.2% vs 83.5%; P = .034) but long-term graft function was similar. Hospitalization rates were higher in patients presenting with ESBL-E-related urinary tract infection (UTI) compared with control subjects with ESBL-E-negative UTI (60.3% vs 31.3%; P = .002) but 5-year graft survival was superior in patients presenting with ESBL-E-related UTI (88.6% vs 69.8%; P = .035) compared with control subjects with ESBL-E-negative UTI. Recurrence rates were similar in patients with or without ESBL-E-related UTI. Initial antibiotic treatment was adequate in 41.2% of patients presenting with ESBL-E-related urosepsis, resulting in a reevaluation of antibiotic stewardship in our clinic. CONCLUSIONS: ESBL-E detection in general was associated with higher mortality, but graft survival in patients with ESBL-E-related UTI was significantly better compared with ESBL-E-negative UTI.

Donor-specific HLA antibodies in a cohort comparing everolimus with cyclosporine after kidney transplantation.

Donor-specific HLA antibodies (DSA) have a negative impact on kidney graft survival. Therefore, we analyzed the occurrence of DSA and antibody-mediated rejection (AMR) in patients from two prospective randomized trials in our center. At 3-4.5 months posttransplant 127 patients were randomized to continue cyclosporine or converted to everolimus therapy. The presence of DSA was prospectively assessed using Luminex assays. AMR was defined according to the Banff 2009 classification. Antibody screening was available in 126 patients with a median follow-up of 1059 days. Seven out of 65 (10.8%) patients on cyclosporine developed DSA after a median of 991 days. In comparison, 14/61 patients (23.0%) randomized to everolimus developed DSA after 551 days (log-rank: p = 0.048). Eight patients on everolimus compared to two patients on cyclosporine developed AMR (log-rank: p = 0.036). Four of 10 patients with AMR-all in the everolimus group-lost their graft. A multivariate regression model revealed everolimus, >3 mismatches and living donor as significant risk factors for DSA. Acute rejection within the first year, >3 mismatches, everolimus and living donor were independent risk factors for AMR. This single center analysis demonstrates for the first time that everolimus-based immunosuppression is associated with an increased risk for the development of DSA and AMR.

Performance of a minimally invasive uncalibrated cardiac output monitoring system (Flotrac/Vigileo) in haemodynamically unstable patients.

BACKGROUND: Early haemodynamic assessment is of particular importance in the evaluation of haemodynamically compromised patients, but is often precluded by the invasiveness and complexity of the established cardiac output (CO) monitoring techniques. The FloTrac/Vigileo system allows minimally invasive CO determination based on the arterial pressure waveform derived from any standard arterial catheter, and the algorithm underlying CO calculation was recently modified to allow a more precise estimate of aortic compliance. METHODS: Using the new software, we studied 25 haemodynamically unstable patients who had a radial artery catheter and underwent invasive haemodynamic monitoring with the PiCCO system. PiCCO-derived transpulmonary thermodilution and pulse contour CO (reference-CO) were compared with the CO values obtained with the FloTrac/Vigileo system (AP-CO). Reported CO values are indexed to body surface area. Agreement between reference-CO and AP-CO recorded during routine clinical care was assessed using Bland-Altman statistics. RESULTS: Overall bias between the reference-CO and the AP-CO (n=324) was 0.68 litre min(-1) m(-2) with a high percentage error of +/- 58.8% (95% limits of agreement +/- 1.94 l min(-1) m(-2)). There was a significant difference (P<0.001) between the radial and the femoral mean arterial pressures, and bias was significantly larger for a mean pressure difference of >5 mm Hg (0.93 vs 0.57 litre min(-1) m(-2), P=0.032). No connection was found between the norepinephrine dose and the CO agreement. CONCLUSIONS: Despite the updated algorithm, AP-CO still showed a limited agreement with the reference-CO and systematically underestimated the CO so that the method is not suitable to replace invasive CO monitoring at present.