Delayed graft function (DGF) remains a major barrier to improved outcomes after kidney transplantation. High-risk transplant recipients can be identified, but no definitive prediction model exists. Novel biomarkers to predict DGF in the first hours post-transplant, such as neutrophil gelatinase-associated lipocalin (NGAL), are under investigation. Donor management to minimize the profound physiological consequences of brain death is highly complex. A hormonal resuscitation package to manage the catecholamine "storm" that follows brain death is recommended. Donor pretreatment with dopamine prior to procurement lowers the rate of DGF. Hypothermic machine perfusion may offer a significant reduction in the rate of DGF vs simple cold storage, but costs need to be evaluated. Surgically, reducing warm ischemia time may be advantageous. Research into recipient preconditioning options has so far not generated clinically helpful interventions. Diagnostic criteria for DGF vary, but requirement for dialysis and/or persistent high serum creatinine is likely to remain key to diagnosis until current work on early biomarkers has progressed further. Management centers on close monitoring of graft (non)function and physiological parameters. With so many unanswered questions, substantial reductions in the toll of DGF in the near future seem unlikely but concentrated research on many levels offers long-term promise.
BackgroundThis study compared the use of static cold storage versus continuous hypothermic machine perfusion in a cohort of kidney transplant recipients at high risk for delayed graft function (DGF).MethodsIn this national, multicenter, and controlled trial, 80 pairs of kidneys recovered from brain-dead deceased donors were randomized to cold storage or machine perfusion, transplanted, and followed up for 12 months. The primary endpoint was the incidence of DGF. Secondary endpoints included the duration of DGF, hospital stay, primary nonfunction, estimated glomerular filtration rate, acute rejection, and allograft and patient survivals.ResultsMean cold ischemia time was high but not different between the 2 groups (25.6 ± 6.6 hours vs 25.05 ± 6.3 hours, 0.937). The incidence of DGF was lower in the machine perfusion compared with cold storage group (61% vs. 45%, P = 0.031). Machine perfusion was independently associated with a reduced risk of DGF (odds ratio, 0.49; 95% confidence interval, 0.26-0.95). Mean estimated glomerular filtration rate tended to be higher at day 28 (40.6 ± 19.9 mL/min per 1.73 m2 vs 49.0 ± 26.9 mL/min per 1.73 m2; P = 0.262) and 1 year (48.3 ± 19.8 mL/min per 1.73 m2 vs 54.4 ± 28.6 mL/min per 1.73 m2; P = 0.201) in the machine perfusion group. No differences in the incidence of acute rejection, primary nonfunction (0% vs 2.5%), graft loss (7.5% vs 10%), or death (8.8% vs 6.3%) were observed.ConclusionsIn this cohort of recipients of deceased donor kidneys with high mean cold ischemia time and high incidence of DGF, the use of continuous machine perfusion was associated with a reduced risk of DGF compared with the traditional cold storage preservation method.
Public health concerns exist surrounding the epidemic of the Zika virus (ZIKV) and the rapid growth of transplantation in developing countries, including endemic zones of active arbovirus transmission, as well as travel to such regions by potential organ donors and recipients. Few data exist regarding the clinical characteristics of ZIKV infection in immunocompromised hosts. Laboratory screening protocols for transplantation to differentiate ZIKV infections from other endemic viral diseases and for the detection of possible donor-derived infection have not been stated. The diagnosis of ZIKV infection remains a challenge, fueled by the lack of standardized commercially available diagnostic tests and validated reference diagnostic laboratories, as well as the limited duration of ZIKV viremia. In this small series, ZIKV infection in renal and liver recipients presented without rash, conjunctivitis, or neurological symptoms, and with abnormal graft function, thrombocytopenia, and bacterial superinfection. We report the first case series of ZIKV infection in solid organ recipients, with a description of clinical and laboratory features and therapeutic management.
Conversion to a sirolimus-based immunosuppression regimen associated with MMF allowed striking renal function recovery in heart transplant recipients with calcineurin inhibitor-induced renal impairment at midterm follow-up.
The therapeutic effect of induced pluripotent stem cells (iPSs) on the progression of chronic kidney disease (CKD) has not yet been demonstrated. In this study, we sought to assess whether treatment with iPSs retards progression of CKD when compared with bone marrow mesenchymal stem cells (BMSCs). Untreated 5/6 nephrectomized rats were compared with CKD animals receiving BMSCs or iPSs. Renal function, histology, immunohistochemistry, and gene expression were studied. Implanted iPSs were tracked by the SRY gene expression analysis. Both treatments minimized elevation in serum creatinine, significantly improved clearance, and slowed down progression of disease. The proteinuria was reduced only in the iPS group. Both treatments reduced glomerulosclerosis, iPSs decreased macrophage infiltration, and TGF-β was reduced in kidneys from the BMSC group. Both types of treatments increased VEGF gene expression, TGF-β was upregulated only in the iPS group, and IL-10 had low expression in both groups. The SRY gene was found in 5/8 rats treated with iPSs. These 5 animals presented tumors with histology and cells highly staining positive for PCNA and Wilms' tumor protein antibody characteristics of Wilms' tumor. These results suggest that iPSs may be efficient to retard progression of CKD but carry the risk of Wilms' tumor development.
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