Pretransplant donor biopsy (PTDB)‐based marginal donor allocation systems to single or dual renal transplantation could increase the use of organs with Kidney Donor Profile Index (KDPI) in the ...highest range (e.g. >80 or >90), whose discard rate approximates 50% in the United States. To test this hypothesis, we retrospectively calculated the KDPI and analyzed the outcomes of 442 marginal kidney transplants (340 single transplants: 278 with a PTDB Remuzzi score <4 median KDPI: 87; interquartile range (IQR): 78–94 and 62 with a score = 4 median KDPI: 87; IQR: 76–93; 102 dual transplants median KDPI: 93; IQR: 86–96) and 248 single standard transplant controls (median KDPI: 36; IQR: 18–51). PTDB‐based allocation of marginal grafts led to a limited discard rate of 15% for kidneys with KDPI of 80–90 and of 37% for kidneys with a KDPI of 91–100. Although 1‐year estimated GFRs were significantly lower in recipients of marginal kidneys (−9.3, −17.9 and −18.8 mL/min, for dual transplants, single kidneys with PTDB score <4 and =4, respectively; p < 0.001), graft survival (median follow‐up 3.3 years) was similar between marginal and standard kidney transplants (hazard ratio: 1.20 95% confidence interval: 0.80–1.79; p = 0.38). In conclusion, PTDB‐based allocation allows the safe transplantation of kidneys with KDPI in the highest range that may otherwise be discarded.
This study shows that the standardized assessment of formalin‐fixed pretransplant biopsies helps recover donors with KDPI in the highest range that would be otherwise discarded, and by providing the expected graft outcomes based on KDPI and pretransplant biopsy, it guides the clinician facing the difficult decision whether to accept or reject these organs. See editorial by Gupta et al on page 2444.
Filamentous bacteriophages are widely used in phage display technology. The most common quantification method is lysis plaque formation test (PFT). This technique has several disadvantages, and only ...quantifies infective phages and is not effective when phagemids are used. We developed a qPCR method directed against the M13 replication origin, which detects between 3.3 × 10
3
and 3.3 × 10
8
viral genome copies with a linearity of
R
2
= 0.9998. Using this method we were able to observe a difference of approximately ten more phages than with the PFT. This difference was not due to the presence of a free genome, which suggests the presence of non-infective particles. Using a DNaseI treatment, we observed the presence of 30% to 40% of unpackaged genome in recombinant phage modified in PIII or PVIII. The qPCR method with a DNase I treatment is an efficient method to quantify the total amount of filamentous phages.
Abstract
Background
Acute heart failure is common after ST-elevation myocardial infarction (STEMI), leading to lung congestion. Speckle tracking echocardiography has increased sensitivity to detect ...subclinical myocardial compliance disorders and may help to better understand the physiopathology in this setting.
Purpose
This study sought to determine the correlation and prognostic ability of admission lung congestion evaluated by lung ultrasound (LUS) and peak atrial longitudinal strain (PALS) performed after the acute phase of STEMI.
Methods
This was a prospective cohort of STEMI patients treated in a tertiary care hospital. LUS was performed by two independent operators before primary percutaneous coronary intervention (PCI). Our protocol consisted of eight scanning sites, which were considered positive for congestion if there were three or more B-lines in at least one site. Echocardiography was performed in all patients 2–4 days after STEMI, and the images were interpreted offline by two operators blinded to LUS findings. PALS <30 was considered abnormally reduced atrial contraction. Major cardiovascular events (MACE) were considered as new myocardial infarction, stroke or death in 30 days.
Results
Of the 339 patients admitted with STEMI, 208 (61%) performed LUS and had interpretable PALS. The mean age was 61 (±12) years and 65% were male. Lung congestion was present in 48% patients. Mean left ventricular ejection fraction (LVEF) was 49%, 21% of patients had EF<40%. Pearson correlation between the number of positive LUS sites and PALS was 0.18 (P=0.029). A subanalysis including only patients with left ventricle ejection fraction >50% showed similar results (correlation 0.10, P=0.349). All 10 (5%) patients with unsuccessful primary PCI had PALS <30. No patients with PALS>30 experienced 30-day MACE, while patients with PALS <30 with and without lung congestion had 1.6% and 13.8% 30-day MACE, respectively.
Conclusion
In a cohort of STEMI patients, the correlation of positive LUS sites and the PALS was low. Impaired PALS was associated with unsuccessful primary PCI, while normal PALS was associated with uneventful follow-up. The PALS assessment in addition to LUS profile was able to identify patients at higher risk for MACE. Although timing difference between lung ultrasound and echocardiography is a limitation of this analysis, our findings are consistent with the “lung water cascade theory”.
Funding Acknowledgement
Type of funding sources: None.
Abstract Despite their contribution in the success of organ transplantation, calcineurin inhibitors (CNIs) may be responsible for frequent and severe side effects that can affect graft survival and ...life expectancy. In this article, we have reviewed registry studies and randomized controlled trials (RCTs) that seek to avoid, withdraw, or minimize CNIs in renal transplant recipients. Attempts to completely avoid CNIs by administering mycophenolate mofetil (MMF) and/or sirolimus (SRL) have resulted in increased risks of rejection and side effects, with small advantage to improve renal graft function. Early withdrawal of CNIs after transplantation using administration of MMF can improve graft function but may be associated with a greater risk of acute or chronic rejection and graft failure. RCTs in which CNIs were replaced a few months after transplantation by SRL reported improved graft function among SRL-treated patients, but such a treatment was complicated by iatrogenic toxicity. Late replacement of CNIs with SRL did not produce a particular advantage and again was complicated by more frequent side effects. On the basis of these trials, it seems that CNI elimination can trigger rejection or side effects. Recent RCTs showed that minimization of CNI doses in association with everolimus does not increase the risk of rejection, allows one to obtain good graft function, and is well tolerated. Such an approach seems therefore preferable to complete elimination of CNIs with substitution of the current immunosuppressive drugs.
Abstract Background Kidney transplant recipients (KTRs) manifest hypercoagulable state that contributes to an increased incidence of deep vein thrombosis (DVT), not only early but also late in their ...course. KTRs display an imbalance of hemostatic mechanisms with a multifactorial rise in procoagulant factors, partly related to traditional risk factors and partly to transplantation. The aim of this study was to evaluate the incidence of first episodes of DVT among KTRs, focusing on risk factors. Methods From 2008 to 2011, we evaluated 30 kidney transplant patients who ≥4 months there after transplantation developed DVT in the lower limbs only, lower limbs complicated by pulmonary embolism or retinal thrombosis. We analyzed causes of primary nephropathy, immunosuppressive regimen, post-transplantation infections, and erythrocytosis. DVT was diagnosed by color Doppler ultrasound or eye examination. Results A significantly increased incidence of DVT was observed among patients receiving cyclosporine or cyclosporine + mammalian target of rapamycin inhibitors, affected by polycystic kidney diseases, systemic lupus erythematosus or nephrotic syndrome, or displaying rapid and/or excessive correction of hematocrit values. DVT was not significantly related to an acute infection (cytomegalovirus) or to the prior dialysis modality. Conclusions Hypercoagulability is a multifactorial condition in KTRs, representing a severe complication in stable patients. Prevention may consist of either accurate pretransplantation screening for thrombophilia or identification of patients at higher DVT risk.
Abstract Introduction It is widely accepted that the risk of malignancies is significantly increased among patients with end-stage kidney disease (ESKD) and after kidney transplantation compared with ...the general population. Only a few data are available on kidney transplantation waiting list patients. The aim of this study was to investigate solid organ cancer incidence among subjects on the waiting list at a single center. Materials and Methods We retrospectively reviewed the records of all patients enrolled on our kidney transplantation waiting list between August 1, 2008 and July 31, 2010, seeking to evaluate the causes of withdrawal from the list, incidence of cancer, type of neoplasm, and its correlation with clinical features. We estimated the ratio of observed to expected numbers of cancers, the standardized incidence ratio (SIR). Results Among 1184 patients, we excluded 569 patients from the waiting list including 26 (4.56%) who displayed malignancies. The overall incidence of cancer was 0.11 events/person-months and the overall prevalence of cancer was 2.2%. In 97% of patients, the malignant disease was confined to the primitive organ of origin without secondary dissemination. We observed a prevalence of cancers related to ESKD (17; 65.38%). The SIR for all cancer types in our population compared with the general population was 2.22. The SIR for native kidney and thyroid cancers among our population compared with the general population was >10. Conclusion The incidence of cancer was significantly increased among kidney transplantation waiting list patients compared with the general population. Our study highlighted the importance of a careful, targeted neoplastic screening. It could be particularly important for ESKD-related malignancies like native kidney tumors or thyroid cancers.
Abstract Background Metabolic syndrome (MS) includes some risk factors for development of diabetes and cardiovascular disease, obesity (BMI > 30), high triglycerides, low HDL cholesterol, ...hypertension and impaired glucose tolerance. Following the definition of the Adult Treatment Panel III criteria, a diagnosis of MS was established when 3 or more factors were present. In renal transplan patients MS has been reported to negatively influence both patient and graft survivals. The present study sought to verify the effect of MS among our cases. Methods 298 cadaveric renal transplant recipients operated between January 1, 1996 and December 31, 2001 with absence of diabetes before transplantation, stable renal function 1 year posttransplantation and at least 4 years follow up were retrospectively evaluated from the end of the first post-operative year. Results 50 patients out of 298 (16,7%) had MS at the beginning of the study, including 37 of them with 3 and 13 with 4 risk factors. Only one patient with MS died of cardiovascular disease. Graft failure was observed in 23.5% MS patients versus 9,7% patients without the Syndrome (p:n.s.) Only Creatinine and the incidence of Cardiovascular Diseases at 4 years were statistically higher in MS patients ( P < .001). Conclusions These results suggested that MS is a risk factor for increasing CVD morbidity and decreased graft function, but early treatment of risk factors as soon as they become apparent can limit the adverse effects on patient and graft survival.
Chronic allograft nephropathy (CAN) is characterized by progressive renal dysfunction leading in many cases to graft loss. The pathogenesis of CAN involves both immune and nonimmune factors. ...Concerning immune factors, one of the most remarkable predictors of CAN is acute rejection, which is associated with a worse prognosis if there are multiple episodes or when late onset occurs. Delayed graft function is also a major risk factor for CAN because of a correlation between late restoration of renal function after transplantation and long-term decreased graft survival. High creatinine levels at 6 months and 1 year after transplantation, proteinuria, viral infections, and cardiovascular risk factors are additional significant parameters for the development of CAN. Recent findings suggest that a high renal segmental arterial resistance index measured by Doppler ultrasonography in intrarenal vessels is associated with poor allograft function. Moreover, the study of patient genetic profile represents a new approach to identify predictive factors for CAN.
Abstract On all kidney waiting lists the 10% to 20% of patients who have antibodies against more than 80% of a panel of HLA antigens (panel reactive antibody PRA >80%) are difficult to transplant. ...The best solution for these patients is to find a compatible donor, ideally a full match, who yields a negative crossmatch test (CMX). If this is not possible, desensitization treatment (high-dose) intravenous immunoglobulin (IVIG) or plasmapheresis (PP) + low-dose IVIG is possible with good results in living donor kidney transplantation mainly if the antibody titer is low. It may also be offered to patients awaiting cadaveric donors too after a long waiting time; however, when applied for several months, it has the obvious disadvantage of giving the patient the risk for long-lasting immunologic weakness without the certitude of finding a kidney. In one of our recent cases of combined liver plus kidney transplantation, a positive CMX became negative 8 hours after the liver operation; the kidney was transplanted with a good result which lasted over 3 years. This observation suggested the possibility of a quick desensitization protocol in selected patients with a large (but not strong) immunization who probably are the majority. Patients sensitized to IVIG and with low titer PRA could be given a single PP + low-dose IVIG (what can be done within the time limit of cadaveric donor kidney transplantation) with good probability of turning an initial positive CMX to negative with the possibility of performing the operation and the advantage of giving the immunosuppression only when the kidney is present.
Cardiovascular disease (CVD) represents the main cause of morbidity and mortality after renal transplantation. In view of the modern paradigm of atherosclerosis as an inflammatory disease, this study ...investigated the impact of inflammatory cytokine polymorphisms on posttransplant CVD.
The association between cytokine polymorphisms and CVD was assessed in a case-control study to identify the differences in genotype distributions between kidney allografts with or without posttransplant CVD. To validate our results in two independent groups, we divided a cohort of 798 renal transplant recipients according to geographic area: an evaluation cohort of 478 patients from Emilia-Romagna and a validation cohort of 320 patients from the rest of Italy. Tumor necrosis factor (TNF)-alpha, transforming growth factor-beta1, interleukin (IL)-10, IL-6, interferon-gamma, and IL-8 polymorphisms were analyzed, and thereafter, the cytokine production genotype was assigned.
In the evaluation cohort, the patients in the CVD and no-CVD groups differed significantly in TNF-alpha and IL-10 genotype frequencies. Using multivariate analyses to test the association with CVD, the TNF-alpha high-producer genotype was associated with a significantly increased cardiovascular risk (odds ratio OR=4.41, 95% confidence interval (CI)=2.53-7.67). Conversely, the IL-10 high-producer genotype resulted protective against CVD (OR=0.07, 95% CI=0.02-0.29). These findings were confirmed in the validation cohort where the carriers of the TNF-alpha high-producer genotype proved to be at 2.45-fold increased cardiovascular risk (OR=2.45, 95% CI=1.29-4.63), whereas the IL-10 high-producer genotype was associated with a 0.08-fold reduced risk (OR=0.08, 95% CI=0.02-0.36).
This work suggests a prognostic value of TNF-alpha and IL-10 genotypes, which might represent cardiovascular risk markers in renal transplant.
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