Mood, body image, fear of kidney failure, life satisfaction, and decisional stability following living kidney donation: Findings from the KDOC study.

Prior studies demonstrate that most living kidney donors (LKDs) report no adverse psychosocial outcomes; however, changes in psychosocial functioning at the individual donor level have not been routinely captured. We studied psychosocial outcomes predonation and at 1, 6, 12, and 24 months postdonation in 193 LKDs and 20 healthy controls (HCs). There was minimal to no mood disturbance, body image concerns, fear of kidney failure, or life dissatisfaction, indicating no incremental changes in these outcomes over time and no significant differences between LKDs and HCs. The incidence of any new-onset adverse outcomes postdonation was as follows: mood disturbance (16%), fear of kidney failure (21%), body image concerns (13%), and life dissatisfaction (10%). Multivariable analyses demonstrated that LKDs with more mood disturbance symptoms, higher anxiety about future kidney health, low body image, and low life satisfaction prior to surgery were at highest risk of these same outcomes postdonation. It is important to note that some LKDs showed improvement in psychosocial functioning from pre- to postdonation. Findings support the balanced presentation of psychosocial risks to potential donors as well as the development of a donor registry to capture psychosocial outcomes beyond the mandatory 2-year follow-up period in the United States.

Collective plasmonic oscillations in gold nanostrips arrays.

Excitation of collective plasmonic modes and their effect on optical behavior are experimentally and theoretically studied in 1D arrays of gold nanostrips in comparison with continuous gold films with periodically modulated profile. In strips, the angular dependence of the reflectivity demonstrates a peak at the resonance condition as opposed to a dip observed in continuous sine wave gratings. In addition, an extremely narrow feature in the reflection is observed in strips and tentatively ascribed to the bright Wood-Rayleigh anomaly. Theoretical calculations based on the combined transfer-matrix coupled-wave analysis and coordinate transformation method are shown to fit the experimental angular and spectral behavior of the plasmonic resonances. The effects are also discussed in terms of a simple equivalent circuit model.

Direct and Indirect Costs Following Living Kidney Donation: Findings From the KDOC Study.

Some living kidney donors (LKDs) incur costs associated with donation, although these costs are not well characterized in the United States. We collected cost data in the 12 mo following donation from 182 LKDs participating in the multicenter prospective Kidney Donor Outcomes Cohort (KDOC) Study. Most LKDs (n = 167, 92%) had one direct cost or more following donation, including ground transportation (86%), health care (41%), meals (53%), medications (36%), lodging (23%), and air transportation (12%). LKDs missed 33 072 total work hours, 40% of which were unpaid and led to $302 175 in lost wages (mean $1660). Caregivers lost $68 655 in wages (mean $377). Although some donors received financial assistance, 89% had a net financial loss in the 12-mo period, with one-third (33%) reporting a loss exceeding $2500. Financial burden was higher for those with greater travel distance to the transplant center (Spearman's ρ = 0.26, p < 0.001), lower household income (Spearman's ρ = -0.25, p < 0.001), and more unpaid work hours missed (Spearman's ρ = 0.52, p < 0.001). Achieving financial neutrality for LKDs must be an immediate priority for the transplant community, governmental agencies, insurance companies, nonprofit organizations, and society at large.

Predonation Direct and Indirect Costs Incurred by Adults Who Donated a Kidney: Findings From the KDOC Study.

Limited information exists on the predonation costs incurred by eventual living kidney donors (LKDs). Expenses related to completion of the donation evaluation were collected from 194 LKDs participating in the multi-center, prospective Kidney Donor Outcomes Cohort (KDOC) Study. Most LKDs (n = 187, 96%) reported one or more direct costs, including ground transportation (80%), healthcare (24%), lodging (17%) and air transportation (14%), totaling $101 484 (USD; mean = $523 ± 942). Excluding paid vacation or sick leave, donor and companion lost wages totaled $35 918 (mean = $187 ± 556) and $14 378 (mean = $76 ± 311), respectively. One-third of LKDs used paid vacation or sick leave to avoid incurring lost wages. Few LKDs reported receiving financial support from the transplant candidate (6%), transplant candidate's family (3%), a nonprofit organization (3%), the National Living Donor Assistance Center (7%), or transplant center (3%). Higher total costs were significantly associated with longer distance traveled to the transplant center (p < 0.001); however, total costs were not associated with age, sex, race/ethnicity, household income, marital status, insurance status, or transplant center. Moderate predonation direct and indirect costs are common for adults who complete the donation evaluation. Potential LKDs should be advised of these possible costs, and the transplant community should examine additional strategies to reimburse donors for them.

Modification of electric and magnetic dipole emission in anisotropic plasmonic systems.

In order to investigate the effects of plasmonic environments on spontaneous emission of magnetic and electric dipoles, we have studied luminescence of Eu³âº ions in close vicinity to gold nanostrip arrays. Significant changes in the emission kinetics, emission polarization, and radiation patterns have been observed in the wavelength range corresponding to the plasmonic resonance. The effect of the plasmonic resonance on the magnetic dipole transition 5D0-->7F1 is found to be very different from its effect on the electric dipole transitions. This makes Eu³âºâ‚‹ containing complexes promising for mapping local distributions of magnetic and electric fields in metamaterials and plasmonic systems.

Kidney allograft biopsy: timing to complications.

BACKGROUND: Clinical Practice guidelines recommend that patients be observed overnight after kidney biopsy based upon data that 1/3 of bleeding complications occur 12 hours post-procedure. Retrospective studies of same day discharge after kidney allograft biopsy suggest this practice may be safe, but no prospective studies to date have examined time to bleeding complications. METHODS: We conducted a single center, prospective, observational study of adult outpatient kidney allograft recipients undergoing elective percutaneous allograft biopsy who were observed for 8 hours post-procedure before discharge home. Bleeding complications were characterized as minor or major and tracked by time post-biopsy. Baseline demographics were assessed for correlation with complications. RESULTS: 8/124 (6.4%) of patients had a bleeding complication and 7/8 (87.5%) of complications occurred within the observation window. 3.2 % were minor and 3.2% were major complications with one major complication occurring after the 8-hour period. Neither the baseline demographics nor drop in serum hemoglobin of > 1 g/dl 6 hours after biopsy predicted a bleeding complication. However, a drop of > 1.5 g/dl correlated with a significant bleeding event (p = 0.006). CONCLUSIONS: An 8-hour observation window captures the majority of bleeding complications after adult kidney transplant biopsy.

Nocardia farcinica pericarditis after kidney transplantation despite prophylaxis.

A deceased-donor kidney transplant recipient developed purulent pericarditis caused by Nocardia despite trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis for Pneumocystis jirovecii. She was treated empirically with ceftriaxone and amikacin and subsequently underwent sternotomy with drainage of an intrapericardial abscess. Culture and susceptibility data demonstrated Nocardia farcinica, which was susceptible to SMX and amikacin, although resistant to ceftriaxone. Nocardia asteroides, the more common human pathogen, is generally susceptible to third-generation cephalosporins and TMP-SMX. N. farcinica is rare in the United States, more virulent and resistant than N. asteroides, and is more likely to cause disseminated disease. Successful therapy of disseminated Nocardia infections is dependent upon choice of appropriate empiric antibiotics in addition to surgical drainage of purulent fluid collections. TMP-SMX prophylaxis may not be sufficient to prevent infections due to Nocardia species in all immunosuppressed transplant recipients. Here, a rare complication of this unusual pathogen is discussed.

Inhibition of allorecognition by a human class II MHC-derived peptide through the induction of apoptosis.

The interaction of the T-cell receptor with the major histocomatibility complex (MHC)-peptide complex is central to T-cell activation. Variation in the nature of the peptide bound within the groove of the MHC molecule may result in an altered T-cell response. Because some naturally processed peptides bound within the groove of the class II MHC molecule are derived from the MHC molecules themselves, we studied the inhibitory effects of synthetic class II MHC peptides on alloimmune responses in vitro. Three peptides derived from a highly conserved region of the class II MHC alpha chains inhibited the rat mixed lymphocyte response (MLR) in a dose-dependent manner, with the human HLA-DQA1 peptide also inhibiting the human and mouse MLR. No effect was seen on mitogen-induced T-cell proliferation. HLA-DQA1 inhibited cytolytic T lymphocyte (CTL) generation in a dose-response fashion, with no reduction in preformed CTL killing, suggesting that the inhibitory effect is targeted at CD4(+) T-cell function. Cell-cycle analysis by flow cytometry showed that restimulation of primed T cells in the presence of HLA-DQA1 resulted in increased apoptosis, whereas unstimulated cells were not affected. These data demonstrate that synthetic peptides derived from highly conserved regions of the class II MHC alpha chain can alter CD4(+) T-lymphocyte alloimmune responses in vitro, and this effect is mediated by the induction of apoptosis in activated T cells.

Regulatory functions of self-restricted MHC class II allopeptide-specific Th2 clones in vivo.

We studied T-cell clones generated from grafts of rejecting and tolerant animals and investigated the regulatory function of Th2 clones in vitro and in vivo. To prevent allograft rejection, we treated LEW strain recipient rats of WF strain kidney grafts with CTLA4Ig to block CD28-B7 costimulation. We then isolated epitope-specific T-cell clones from the engrafted tissue, using a donor-derived immunodominant class II MHC allopeptide presented by recipient antigen-presenting cells. Acutely rejected tissue from untreated animals yielded self-restricted, allopeptide-specific T-cell clones that produced IFN-gamma, whereas clones from tolerant animals produced IL-4 and IL-10. Adoptive transfer into naive recipients of Th1 clones, but not Th2 clones, induced alloantigen-specific delayed-type hypersensitivity (DTH) responses. In addition, Th2 clones suppressed DTH responses mediated by Th1 clones in vivo and blocked Th1 cell proliferation and IFN-gamma production in vitro. A pilot human study showed that HLA-DR allopeptide-specific T-cell clones generated from patients with chronic rejection secrete Th1 cytokines, whereas those from patients with stable graft function produce Th2 cytokines in response to donor-specific HLA-DR allopeptides. We suggest that self-restricted alloantigen-specific Th2 clones may regulate the alloimmune responses and promote long-term allograft survival and tolerance.

Association between irisin and major chronic diseases: a review.

OBJECTIVE: Irisin is a muscle-secreted protein released into the circulation by cleavage of fibronectin type III domain containing protein 5(FNDC5). Since its discovery in 2012, it has been the subject of many researches due to its physiological role. It is believed that understanding irisin's function may be the key to comprehend many diseases and their development. The aim of this study is to perform a systematic review in order to establish whether there is an association of irisin's levels with obesity, diabetes mellitus, non-alcoholic steatohepatitis, chronic kidney disease and cancer in terms of prognosis. MATERIALS AND METHODS: The articles that support these findings were selected from Medline using the keyword "irisin" and filtered with "humans only". The selected articles were in English and with abstract. RESULTS: Higher baseline irisin concentrations are associated with greater reductions in glycemia and insulinemia after weight loss in obese subjects. Besides, it was observed that macrovascular disease, a complication of diabetes, was developed when there were lower levels of irisin. In addition, although not statistically significant, high levels of irisin were associated with portal inflammation and severity of histological lesions. Its concentrations decreased with increasing chronic kidney disease stage, and they were not only independently and positively predicted by renal function and insulin resistance but also associated with sarcopenia and carotid atherosclerosis in patients undergoing peritoneal dialysis. Regarding cancer, irisin reduced the proliferation, viability and migration of malignant breast cells. Finally, it is also related to bone health once its concentration is associated with previous osteoporotic fractures. CONCLUSIONS: In every condition studied, irisin's concentrations were related to the development of the disease.

Role of indirect allorecognition in experimental late acute rejection.

BACKGROUND: Late acute rejection affects up to 28% of renal allograft recipients and remains a major risk factor for late graft loss. As donor-origin antigen-presenting cells are depleted with time, T-cell recognition of donor-derived alloantigenic peptides presented by self antigen-presenting cells (the "indirect pathway" of allorecognition) may play a key role in the initiation of late acute rejection episodes. METHODS: To test this hypothesis, we developed a clinically relevant experimental model in the rat (Wistar-Furth/Lewis) in which allograft recipients received cyclosporine for 1 month after transplantation and were then allowed to reject the graft upon discontinuation of immunosuppression. Lymphocyte proliferation assays to synthetic class II MHC allopeptides of donor origin and also to intact donor (Wistar-Furth) cells were performed at this time. The effector mechanisms studied included delayed-type hypersensitivity (DTH) responses, lymphocyte-mediated cytotoxicity, and alloantibody production. RESULTS: Lymphocytes from recipients undergoing late acute rejection had marked suppression of mixed lymphocyte reaction proliferation to intact donor cells. Significant proliferation to donor-derived 25-mer polymorphic class II MHC allopeptides was elicited, however. In vivo, significant DTH responses were observed to both MHC allopeptides and intact Wistar-Furth cells. Recipient lymphocytes also exhibited significant killing of donor cells, although not third-party cells, and anti-donor alloantibodies were detected by flow cytometry. CONCLUSION: Our results indicate that T cells primed via the indirect pathway are present during acute rejection that occurs after discontinuation of cyclosporine. Mixed lymphocyte reactivity is markedly reduced at this time. Furthermore, there is an association between such allopeptide-primed T cells and the elicitation of specific DTH responses and provision of help to B cells to produce alloantibodies and activation of CD8+ T cells to become effector cytotoxic cells.

Indirect allorecognition of major histocompatibility complex allopeptides in human renal transplant recipients with chronic graft dysfunction.

BACKGROUND: It has been suggested that T cells primed by processed donor major histocompatibility complex antigen (the "indirect" pathway of allorecognition) may be responsible for mediating chronic allograft rejection. The purpose of this study was to develop a clinically useful assay to study the occurrence of indirect allorecognition during chronic rejection in humans. METHODS: A panel of 20 mer peptides corresponding to the hypervariable regions of HLA-DRB1*0101, DRB1*1501, and DRB1*0301 were synthesized. Lymphocytes obtained from renal allograft recipients were cocultured with these peptides. Proliferation was assayed by DNA incorporation of [3H]thymidine, and positive proliferation was defined by a statistically significant increase in counts per minute over background with a minimum stimulation index of 2. The precursor frequency of allopeptide reactive T cells was determined by limiting dilution analysis. RESULTS: Lymphocytes from 82% of patients who were mismatched for at least one of the three DR molecules and had chronic allograft dysfunction specifically proliferated to the mismatched allopeptides (n=11). Proliferation was seen in only 6% of control subjects (2/33, P<0.0001). The proliferative response was low grade and was best detected on day 7-8 of culture in vitro. The precursor frequency of peptide-specific T cells was more than 10-fold higher compared with controls (P<0.001). CONCLUSIONS: These data demonstrate for the first time that T cells of patients with chronic graft dysfunction are primed to recognize and respond to specific donor-derived major histocompatibility complex allopeptides. Our results support the hypothesis that T cells primed via the indirect pathway of allorecognition may be important mediators of chronic rejection and provide the rationale to develop specific therapeutic strategies to prevent or interrupt this process.

Cellular and humoral mechanisms of vascularized allograft rejection induced by indirect recognition of donor MHC allopeptides.

INTRODUCTION: To investigate the role and mechanisms of indirect allorecognition in allograft rejection, we studied whether priming T cells with donor-derived MHC allopeptides could accelerate rejection in a vascularized allograft model. METHODS: Lewis recipients of fully mismatched Wistar Furth cardiac allografts were immunized before transplantation with donor MHC allopeptides. RESULTS: Animals immunized with immunogenic class II MHC allopeptides rejected their grafts in a significantly accelerated fashion compared with controls. Additional studies demonstrated that a single immunodominant RT1.D (HLA-DR like) allopeptide was responsible for accelerating the rejection process. Histological analysis of rejected allografts revealed marked vascular rejection in the accelerated, although not the control, group as well as severe cellular rejection. Peak production of IgM and IgG donor-specific alloantibodies was detected by flow cytometry 1 week earlier in the sera of the accelerated group compared with the control group. Immunohistological analysis of grafts from the accelerated compared with the control group showed increased endothelial deposition of IgG2b, C3, and fibrin, and up-regulation of class II MHC molecule expression. Increased intragraft expression of interferon-y and the interferon-gamma-induced chemokines, inducible protein-10 and Mig, and infiltration by activated mononuclear cells expressing CXCR3, the receptor for inducible protein-10 and Mig, was also seen. CONCLUSION: These novel data provide evidence of a definitive link between indirect allorecognition of donor-derived MHC class II peptides and the cellular and humoral mechanisms of vascularized allograft rejection.

Chronic allograft dysfunction: mechanisms and new approaches to therapy.

Renal allograft failure is the most common cause of end-stage renal disease beyond the early posttransplantation period, accounting for 25% to 30% of patients awaiting renal transplantation. Despite recent advances in immunosuppressive therapy, improvements in long-term graft survival have not been commensurate with those observed in 1-year graft survival. The most common cause of chronic allograft loss is an incompletely understood clinicopathological entity sometimes called chronic rejection, chronic allograft dysfunction or in the case of kidneys, chronic allograft nephropathy. Although the precise mechanism(s) responsible for the characteristic pathological changes are still unclear, it is generally agreed that both alloantigen-dependent and alloantigen-independent factors influence the development of chronic allograft nephropathy. This article will address the potential mechanisms responsible for the pathogenesis of chronic dysfunction in solid organ grafts and the current approaches to management, including newer therapies designed to prevent the progression of the disease.

Glomerulonephritis after ventriculo-atrial shunt.

We describe five patients with glomerulonephritis (GN) associated with cerebrospinal fluid shunt insertion to relieve hydrocephalus. A ventriculo-atrial (V-A) shunt had been placed on average 12.5 years prior to the diagnosis of nephritis (range 0.5-21 years). Four patients developed membranoproliferative glomerulonephritis (MPGN) with associated hypocomplementaemia. A single patient developed focal proliferative glomerulonephritis. Coagulase-negative staphylococci were cultured in four patients, either from blood or from the shunt. Four patients had their shunts removed, two of whom also received antibiotics. The other patient received antibiotics alone for infective endocarditis due to staphylococcal bacteraemia which originated in the shunt. All patients had substantial renal impairment at the time of diagnosis (GFR, glomerular filtration rate, 20-45 ml/min). There was significant improvement in renal function after appropriate treatment; four of the five patients doubled their GFRs and two patients regained normal function.

The rapid reversal of profound hypothermia using peritoneal dialysis.

Severe hypothermia is associated with serious patient morbidity and mortality. The groups most frequently affected are the elderly, the very young and substance abusers. We describe three such cases which were successfully treated using warmed peritoneal dialysis. Two patients recovered completely and were left with no long term deficits. The third patient recovered from the acute event, but succumbed later to an underlying medical condition. Warmed peritoneal lavage is an efficient, cost effective approach which is easily performed without specialist equipment, and involves minimal risk to the patient.

[Lipoprotein(a) and other lipid parameters in cord blood: a study of 528 cases]. / Lipoprotéine (a) et autres paramètres lipidiques dans le sang de cordon: une étude de 528 cas.

We have studied the concentrations of cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoproteins A-I and B, and lipoprotein (a) in cord blood, from children born in our hospital for a five-month period. Cholesterol and triglycerides values were slightly lower than values obtained in cord blood within other populations. The distribution of lipoprotein (a) concentrations was markedly skewed towards low values (mean = 1.74 mg/dl, median = 1 mg/dl), similar to that of other young or adult Caucasian populations. Children with a positive familial history of cardiovascular heart disease had a higher mean lipoprotein level (a), and a higher prevalence of lipoprotein values exceeding 5 mg/dl, than children with a negative familial history. These results suggest that lipoprotein (a) is an important risk factor for cardiovascular heart disease.

Renal revascularisation by gastroduodenal-renal bypass as treatment of renal artery stenosis.

We report the case of a 63 year old hypertensive male who presented with acute renal failure following treatment of his hypertension with the ACE antagonist, captopril. He was documented to have bilateral renal artery stenosis, which was treated by left renal artery angioplasty and revascularisation of the right kidney by anastomosis of the right renal artery to the superior gastroduodenal branch of the hepatic artery. Postoperatively, he made an excellent recovery, with restoration of his renal function to normal and improved control of his hypertension.