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1.
Am J Transplant ; 18(8): 1966-1976, 2018 08.
Article in English | MEDLINE | ID: mdl-29380523

ABSTRACT

Insufficient hemodynamics during agonal phase-ie, the period between withdrawal of life-sustaining treatment and circulatory arrest-in Maastricht category III circulatory-death donors (DCD) potentially exacerbate ischemia/reperfusion injury. We included 409 Dutch adult recipients of DCD donor kidneys transplanted between 2006 and 2014. Peripheral oxygen saturation (SpO2-with pulse oximetry at the fingertip) and systolic blood pressure (SBP-with arterial catheter) were measured during agonal phase, and were dichotomized into minutes of SpO2 > 60% or SpO2 < 60%, and minutes of SBP > 80 mmHg or SBP < 80 mmHg. Outcome measures were and primary non-function (PNF), delayed graft function (DGF), and three-year graft survival. Primary non-function (PNF) rate was 6.6%, delayed graft function (DGF) rate was 67%, and graft survival at three years was 76%. Longer periods of agonal phase (median 16 min [IQR 11-23]) contributed significantly to an increased risk of DGF (P = .012), but not to PNF (P = .071) and graft failure (P = .528). Multiple logistic regression analysis showed that an increase from 7 to 20 minutes in period of SBP < 80 mmHg was associated with 2.19 times the odds (95% CI 1.08-4.46, P = .030) for DGF. In conclusion, duration of agonal phase is associated with early transplant outcome. SBP < 80 mmHg during agonal phase shows a better discrimination for transplant outcome than SpO2 < 60% does.


Subject(s)
Delayed Graft Function/mortality , Graft Rejection/mortality , Hemodynamics , Kidney Failure, Chronic/surgery , Kidney Transplantation/mortality , Tissue Donors/supply & distribution , Tissue and Organ Procurement/methods , Adult , Blood Pressure , Death , Delayed Graft Function/etiology , Donor Selection , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Survival , Humans , Kidney Transplantation/adverse effects , Male , Middle Aged , Oxygen/metabolism , Perfusion , Postoperative Complications , Prognosis , Retrospective Studies , Risk Factors , Survival Rate , Systole
2.
Am J Transplant ; 17(4): 1020-1030, 2017 04.
Article in English | MEDLINE | ID: mdl-27639190

ABSTRACT

In renal transplantation, use of calcineurin inhibitors (CNIs) is associated with nephrotoxicity and immunosuppression with malignancies and infections. This trial aimed to minimize CNI exposure and total immunosuppression while maintaining efficacy. We performed a randomized controlled, open-label multicenter trial with early cyclosporine A (CsA) elimination. Patients started with basiliximab, prednisolone (P), mycophenolate sodium (MPS), and CsA. At 6 months, immunosuppression was tapered to P/CsA, P/MPS, or P/everolimus (EVL). Primary outcomes were renal fibrosis and inflammation. Secondary outcomes were estimated glomerular filtration rate (eGFR) and incidence of rejection at 24 months. The P/MPS arm was prematurely halted. The trial continued with P/CsA (N = 89) and P/EVL (N = 96). Interstitial fibrosis and inflammation were significantly decreased and the eGFR was significantly higher in the P/EVL arm. Cumulative rejection rates were 13% (P/EVL) and 19% (P/CsA), (p = 0.08). A post hoc analysis of HLA and donor-specific antibodies at 1 year after transplantation revealed no differences. An individualized immunosuppressive strategy of early CNI elimination to dual therapy with everolimus was associated with decreased allograft fibrosis, preserved allograft function, and good efficacy, but also with more serious adverse events and discontinuation. This can be a valuable alternative regimen in patients suffering from CNI toxicity.


Subject(s)
Everolimus/therapeutic use , Fibrosis/drug therapy , Graft Rejection/drug therapy , Graft Survival/drug effects , Kidney Transplantation/adverse effects , Prednisolone/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Female , Fibrosis/etiology , Graft Rejection/etiology , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Prospective Studies , Time Factors , Weaning
3.
Transpl Infect Dis ; 18(5): 647-660, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27380002

ABSTRACT

BACKGROUND: The impact of allograft pyelonephritis (AGPN) on renal allograft function is controversial. In this study, we evaluated the incidence, risk factors, and the impact of AGPN on renal allograft function. METHODS: Retrospective cohort study in adult renal allograft recipients with 1-year follow-up after transplantation (Tx). Renal allograft function was evaluated by estimated glomerular filtration rate (eGFR) (by Modification of Diet in Renal Disease formula) and 24-h urine protein excretion. RESULTS: A total of 431 renal allograft recipients were analyzed; 57 (13.2%) developed AGPN within 1 year after Tx. Median time between Tx and AGPN was 50 days. Risk factors for AGPN were the presence of a urological catheter (odds ratio [OR] = 18.93, 95% confidence interval [CI] = 8.00-44.81, P < 0.001) and preceding asymptomatic bacteriuria (ASB) (OR = 2.16, 95% CI = 1.20-3.90, P = 0.009). In 72.7%, the causative microorganism of ASB was identical to that of the succeeding AGPN episode. Multivariable linear regression analysis showed that experiencing AGPN did not decrease the eGFR (P = 0.61) nor did increased proteinuria (P = 0.29) 1 year after Tx. For the eGFR, an interaction was found between AGPN/bacteriuria (BU) and acute rejection (AR): the group experiencing BU preceding AR had significantly (P < 0.001) lower eGFR compared with the group that experienced only AR (21 mL/min/1.73 m2 vs. 48 mL/min/1.73 m2 ), as a result of increased prevalence of combined rejections within the BU group. CONCLUSION: Indwelling urological catheters and preceding ASB are associated with developing AGPN. An incident of AGPN itself does not impair renal allograft function 1 year after Tx. However, a relevant interaction occurs between BU and AR, in which the sequence of occurrence of these 2 events synergistically impairs the eGFR.


Subject(s)
Allografts/pathology , Bacteriuria/complications , Catheters, Indwelling/adverse effects , Graft Rejection/epidemiology , Kidney Transplantation/adverse effects , Pyelonephritis/complications , Urinary Catheters/adverse effects , Adult , Bacteriuria/microbiology , Female , Glomerular Filtration Rate , Graft Rejection/etiology , Humans , Incidence , Kidney , Male , Middle Aged , Proteinuria/epidemiology , Proteinuria/etiology , Pyelonephritis/epidemiology , Pyelonephritis/etiology , Pyelonephritis/microbiology , Retrospective Studies , Risk Factors , Transplantation, Homologous/adverse effects
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