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Weekend surgery may be associated with a higher risk of early complications, but the effect of the timing of kidney transplant surgery on early allograft outcome remains uncertain. The aim of this study is to evaluate whether the association between weekend transplant surgery and allograft failure was modified by prevalent vascular disease. Using data from the Australia and New Zealand Dialysis and Transplant registry, we examined the association between weekend status and 90-day and 1-year allograft failure in deceased donor transplant recipients between 1994-2012. Two-way interaction between vascular disease and weekend status was examined. Of 6622 recipients, 1868 (28.2%) received transplants during weekends. Compared with weekday transplants, weekend transplants were associated with an adjusted hazard ratio (HR) for 90-day and 1-year allograft failure of 0.99 (0.78-1.25; P = 0.917) and 0.93 (0.76-1.13, P = 0.468), respectively. There was a significant interaction between prevalent vascular disease and weekend status for 90-day allograft failure (Pinteraction = 0.008) but not at 1-year, such that patients with vascular disease were more likely to experience 90-day allograft failure if transplanted on weekend (versus weekdays), particularly failures secondary to vascular complications. Timing of transplantation does not impact on allograft outcome, although those with vascular disease may benefit from more intensive post-transplant follow-up for potential vascular complications.
Assuntos
Transplante de Rim/efeitos adversos , Adulto , Idoso , Estudos de Coortes , Feminino , Rejeição de Enxerto/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Transplante Homólogo , Doenças Vasculares/etiologiaRESUMO
Noninherited maternal human leukocyte antigens may be less detrimental on allograft outcomes after kidney transplantation compared with noninherited paternal antigens, but this association in the era of modern immunosuppression remains unknown. Here we determine the association between parental donor kidneys, acute rejection, and graft failure in primary live-donor parental kidney transplant recipients using data from the Australia and New Zealand Dialysis and Transplant Registry between 1997 and 2012. Of the 1139 recipients followed for a median of 7.2 years (8588 person-years), 652 received kidneys from maternal donors. Compared with paternal donor kidneys, maternal donor kidneys were associated with a significantly increased risk of acute rejection (adjusted odds ratio 1.54; 95% confidence interval [CI], 1.14-2.07) and significant overall graft loss. The latter was confined to recipients who have experienced acute rejection (adjusted hazard ratio 1.60; 95%CI, 1.05-2.43) but not in those who did not experience acute rejection. Thus, our study suggests that recipients of maternal donor kidneys have a greater risk of rejection and graft loss. Hence, clinicians and patients should be cognizant of this association when determining which of the 2 parental donors is most suitable for transplantation.
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Pai , Rejeição de Enxerto/etiologia , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Doadores Vivos , Mães , Doença Aguda , Adolescente , Adulto , Austrália , Criança , Seleção do Doador , Feminino , Rejeição de Enxerto/diagnóstico , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Interferon-γ (IFN-γ)-preactivated mesenchymal stem cells (MSC-γ) are highly immunosuppressive but immunogenic in vivo due to their inherent expression of major histocompatibility (MHC) molecules. Here, we present an improved approach where we modified human bone marrow-derived MSC with interleukin-17A (MSC-17) to enhance T cell immunosuppression but not their immunogenicity. MSC-17, unlike MSC-γ, showed no induction or upregulation of MHC class I, MHC class II, and T cell costimulatory molecule CD40, but maintained normal MSC morphology and phenotypic marker expression. When cocultured with phytohemagglutinin (PHA)-activated human T cells, MSCs-17 were potent suppressors of T cell proliferation. Furthermore, MSC-17 inhibited surface CD25 expression and suppressed the elaboration of Th1 cytokines, IFN-γ, tumor necrosis factor-α (TNF-α), and IL-2 when compared with untreated MSCs (UT-MSCs). T cell suppression by MSC-17 correlated with increased IL-6 but not with indoleamine 2,3-dioxygenase 1, cyclooxygenase 1, and transforming growth factor ß-1. MSC-17 but not MSC-γ consistently induced CD4(+) CD25(high) CD127(low) FoxP3(+) regulatory T cells (iTregs) from PHA-activated CD4(+) CD25(-) T cells. MSC-induced iTregs expressed CD39, CD73, CD69, OX40, cytotoxic T-lymphocyte associated antigen-4 (CTLA-4), and glucocorticoid-induced TNFR-related protein (GITR). These suppressive MSCs-17 can engender Tregs to potently suppress T cell activation with minimal immunogenicity and thus represent a superior T cell immunomodulator for clinical application.
Assuntos
Fatores Imunológicos/imunologia , Fatores Imunológicos/farmacologia , Interleucina-17/imunologia , Interleucina-17/farmacologia , Células-Tronco Mesenquimais/imunologia , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismoAssuntos
Pancreatectomia/métodos , Pancreatite Crônica/genética , Pancreatite Crônica/cirurgia , Tripsina/genética , Adolescente , Criança , Feminino , Humanos , Incidência , Transplante das Ilhotas Pancreáticas/métodos , Masculino , Mutação , Pancreatectomia/estatística & dados numéricos , Pancreatite Crônica/epidemiologia , Pancreatite Crônica/etiologia , Austrália do Sul/epidemiologia , Transplante Autólogo , Resultado do TratamentoRESUMO
PURPOSE OF REVIEW: Rapid advances in bioprinting have attracted the attention of the clinical world. The advent of printable, cytocompatible materials and appropriate hardware provides an unprecedented ability to design and create 3D structures throughout which living cells and bioactive components are strategically distributed. Here, we review those advances and present how they can be used to create new structures for more effective islet cell transplantation. RECENT FINDINGS: There is a need for improvements in the delivery vehicle for transplantable islet cells. Significant progress has been made in 3D printing of multicellular structures and vascularized structures and multiple bioactive molecules. Strategies for extending these recent findings to islet transplantation are discussed. More importantly, the first promising step, 3D printing human islets has recently been demonstrated. SUMMARY: The advent of 3D bioprinting provides unprecedented opportunities for islet transplantation. Highlighting the capabilities of 3D bioprinting should also encourage clinicians to consider other areas appropriate for its use.
Assuntos
Materiais Biocompatíveis/uso terapêutico , Bioimpressão/métodos , Transplante das Ilhotas Pancreáticas/métodos , HumanosRESUMO
Reducing immunosuppression has been proposed as a means of preventing cancer in kidney transplant recipients but this can precipitate graft rejection. Here we tested whether anti-tumor natural killer (NK) cell and allo-responsive T-cell function in kidney transplant recipients may predict cancer risk and define risk of rejection. NK cell function was measured by the release of lactate dehydrogenase and T-cell allo-response by interferon-γ quantification using a panel of reactive T-cell enzyme-linked immunospot (ELISPOT) in 56 kidney transplant recipients with current or past cancer and 26 kidney transplant recipients without cancer. NK function was significantly impaired and the allo-response was significantly lower in kidney transplant recipients with cancer. With prospective follow-up, kidney transplant recipients with poor NK cell function had a hazard ratio of 2.1 (95% confidence interval 0.97-5.00) for the combined end point of metastatic cancer, cancer-related death, or septic death. Kidney transplant recipients with low interferon-γ release were also more likely to reach this combined end point. Thus, posttransplant monitoring of allo-immunity and NK cell function is useful for assessing the risk of over immunosuppression for the development of malignancy and/or death from cancer or sepsis.
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Nocardiosis is a potentially life-threatening disease in renal transplant recipients. It is an uncommon infection with high lethality if left untreated. We report a case of a 67 year-old kidney transplant recipient who developed pulmonary nocardiosis and presented with pleural effusion along with an underlying lung mass, which was successfully treated with trimethoprim-sulphamethoxazole in conjunction with a reduction in immunosuppressive therapy. Five months later, graft function remains stable with complete regression of radiological abnormalities and absence of symptoms. Nocardiosis should be suspected in the presence of pulmonary symptoms in a transplant patient with unusual radiological presentation.
Assuntos
Transplante de Rim/efeitos adversos , Nocardiose/microbiologia , Infecções Oportunistas/microbiologia , Infecções Respiratórias/microbiologia , Nódulo Pulmonar Solitário/microbiologia , Idoso , Antibacterianos/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Masculino , Nocardiose/diagnóstico por imagem , Nocardiose/tratamento farmacológico , Infecções Oportunistas/diagnóstico por imagem , Infecções Oportunistas/tratamento farmacológico , Derrame Pleural/microbiologia , Infecções Respiratórias/diagnóstico por imagem , Infecções Respiratórias/tratamento farmacológico , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/tratamento farmacológico , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoRESUMO
Atypical non HLA antibodies are increasingly recognised as causes of immunological injury in allotransplantation. In this report we describe a non HLA sensitized male renal allograft recipient who developed acute vascular rejection on a "for cause" biopsy (Banff v2, g2, ptc 3) at day 4 post first renal allograft in the presence of elevated angiotensin II type 1 receptor antibodies (AT1R-Ab level 14.1). The acute rejection was treated with pulse corticosteroid therapy, anti-thymocyte globulin (ATG × 6), plasma exchange (1.5 plasma volume replacement x6) and oral candesartan. Serum creatinine improved and follow up biopsy confirmed resolution of rejection following treatment. AT1R-Ab should be considered when rejection is diagnosed in the absence of HLA antibodies.
Assuntos
Autoanticorpos/sangue , Rejeição de Enxerto/imunologia , Transplante de Rim/efeitos adversos , Receptor Tipo 1 de Angiotensina/imunologia , Doença Aguda , Administração Oral , Corticosteroides/administração & dosagem , Adulto , Aloenxertos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Soro Antilinfocitário/administração & dosagem , Benzimidazóis/administração & dosagem , Biópsia , Compostos de Bifenilo , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/terapia , Humanos , Imunossupressores/administração & dosagem , Masculino , Troca Plasmática , Pulsoterapia , Receptor Tipo 1 de Angiotensina/efeitos dos fármacos , Índice de Gravidade de Doença , Tetrazóis/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Regulação para CimaRESUMO
High regulatory T-cell (Treg) numbers predict recurrent cutaneous squamous cell carcinoma in kidney transplant recipients, and the Treg immune phenotype may identify kidney transplant recipients at risk of developing squamous cell carcinoma and/or solid-organ cancer. To investigate this, a total of 116 kidney transplant recipients, of whom 65 had current or past cancer, were immune-phenotyped and followed up prospectively for a median of 15 months. Higher Treg (CD3+CD4+FOXP3+CD25(Hi)CD127(Lo)) proportion and numbers significantly increased the odds of developing cancer (odds ratios (95% CI) 1.61 (1.17-2.20) and 1.03 (1.00-1.06), respectively) after adjusting for age, gender, and duration of immunosuppression. Class-switched memory B cells (CD19+CD27+IgD-) had a significant association to cancer, 1.04 (1.00-1.07). Receiver operator characteristic (ROC) curves for squamous cell carcinoma development within 100 days of immune phenotyping were significant for Tregs, memory B cells, and γδ T cells (AUC of 0.78, 0.68, and 0.65, respectively). After cancer resection, Treg, NK cell, and γδ T-cell numbers fell significantly. Immune-phenotype profiles associated with both squamous cell carcinoma and solid-organ cancer in kidney transplant recipients and depended on the presence of cancer tissue. Thus, immune profiling could be used to stratify kidney transplant recipients at risk of developing cancers to identify those who could qualify for prevention therapy.
Assuntos
Transplante de Rim/efeitos adversos , Neoplasias/etiologia , Neoplasias/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Linfócitos B/imunologia , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/imunologia , Estudos de Coortes , Feminino , Humanos , Memória Imunológica , Imunofenotipagem , Imunossupressores/efeitos adversos , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/imunologia , Neoplasias/prevenção & controle , Razão de Chances , Estudos Prospectivos , Fatores de Risco , Método Simples-Cego , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/imunologiaAssuntos
Transplante de Rim/estatística & dados numéricos , Turismo Médico/estatística & dados numéricos , Nefrologistas/estatística & dados numéricos , Nefrologia/organização & administração , Austrália , Coleta de Dados/normas , Humanos , Nefrologistas/organização & administração , Nefrologia/estatística & dados numéricos , ViagemRESUMO
The history of renal replacement therapy (RRT) for end-stage kidney disease (ESKD) started in 1960 and has reached, in these six decades, goals initially unforeseen. This report describes two patients who commenced dialysis at the age of 17 and 27, for 53 and 45 years, respectively, whereby the modality of RRT was mostly in the form of home haemodialysis. The history of these two patients, who started RRT in distant parts of the world, Australia and Croatia, highlights not only the advances made over time, to significantly delay the onset and reduce the morbidity and mortality associated with ESKD, but also underlines the importance of empowerment and commitment, added values in home haemodialysis.
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The New world primates (NWP) Callithrix jacchus separated from man approximately 50 million years ago and is a potential alternative small non-human primate model for diabetes research. Ultrastructure, and gene expression of pancreatic islets and the recently described diabetes auto antigenic zinc transporters families in human, NWP and pig pancreas were studied. Morphologically NWP islets were larger than pig islets and similar in size to human islets. NWP islets alpha cells had high dense core surrounded by a limiting membrane, beta cells by the mixed morphology of the granule core, and delta cells by moderate opaque core. Antibody staining for insulin, glucagon, somatostatin and Glucagon-like peptide-1 (GLP-1) showed that the distribution pattern of the different cell types within islets was comparable to pig and human islets. In all three species protein expression of zinc transporter ZnT8 was detected in most of the insulin producing beta cells whereas Zip14 expression was widely expressed in alpha and beta cells. In both human and NWP little or no expression of Glut2 was observed compared to Glut1 and glucokinase at the protein level, however the messenger RNA level of Glut2 was greater than Glut1 and glucokinase. In contrast all three glucose transporters were expressed in pig islets at the protein level. The expression of Zip14 in islets is reported for the first time. In conclusion NWP pancreatic islets express comparable islet cell types and distribution to humans and pigs. Importantly, marmosets have a similar glucose transporter profile to humans, making this non-endangered primate species a useful animal model for pancreatic biology.
Assuntos
Callithrix/metabolismo , Proteínas de Transporte/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Ilhotas Pancreáticas/metabolismo , Animais , Proteínas de Transporte/genética , Imunofluorescência , Proteínas Facilitadoras de Transporte de Glucose/genética , Transportador de Glucose Tipo 2/genética , Transportador de Glucose Tipo 2/metabolismo , Humanos , Ilhotas Pancreáticas/ultraestrutura , Microscopia Eletrônica , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: Cardiovascular events remain a major cause of death in kidney transplant recipients. The optimal noninvasive workup to prevent peritransplant cardiac mortality remains contentious. METHODS: We conducted a retrospective analysis to assess the renal transplantation cardiovascular assessment protocol within a single-center population over a 5-year period. Asymptomatic patients aged less than 45 years with no history of cigarette smoking, without diabetes mellitus, and dialysis-dependent for less than 24 months did not undergo cardiac testing before listing. All other asymptomatic patients underwent a noninvasive, tachycardia-induced stress test, where a target heart rate of 85% predicted for age and gender was required. The primary endpoints were rates of acute myocardial infarction (AMI) and cardiovascular death at 30 days after renal transplantation. RESULTS: Between 2015 and 2019, 380 recipients underwent cardiac evaluation: 79 (20.8%) were deemed low cardiovascular risk and placed on the renal transplant waitlist without further assessment; 270 (71.1%) underwent a tachycardia-induced stress test; and 31 (8.1%) were deemed high risk and proceeded directly to invasive coronary angiography (ICA). In the 5-year follow-up, 3 patients (0.8%) experienced an AMI 30 days after renal transplantation, all of which occurred in the high-risk "direct to ICA" cohort. No events were documented in the low-risk cohort or in patients who had a negative tachycardia-induced stress test. There were no cardiovascular deaths within 30 days after transplantation. CONCLUSION: A negative tachycardia-induced cardiac stress test, achieving 85% of predicted heart rate, was associated with a 0% AMI rate and no cardiovascular deaths at 30 days after renal transplantation.
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Background: The long-term effects of arteriovenous fistula (AVF) ligation on cardiovascular structure following kidney transplantation remain uncertain. A prospective randomized, controlled trial (RCT) examined the effect of AVF ligation at 6 months on cardiovascular magnetic resonance imaging (CMR)-derived parameters in 27 kidney transplant recipients compared with 27 controls. A mean decrease in left ventricular mass (LVM) of 22.1 g (95% CI, 15.0 to 29.1) was observed compared with an increase of 1.2 g (95% CI, -4.8 to 7.2) in the control group (P<0.001). We conducted a long-term follow-up observational cohort study in the treated cohort to determine the evolution of CMR-derived parameters compared with those documented at 6 months post-AVF ligation. Methods: We performed CMR at long-term follow-up in the AVF ligation observational cohort from our original RCT published in 2019. Results were compared with CMR at 6 months postintervention. The coprimary end point was the change in CMR-derived LVM and LVM index at long-term follow-up from imaging at 6 months postindex procedure. Results: At a median of 5.1 years (interquartile range, 4.7-5.5 years), 17 patients in the AVF ligation group were studied with repeat CMR with a median duration to follow-up imaging of 5.1 years (IQR, 4.7-5.5 years). Statistically significant further reductions in LVM (-17.6±23.0 g, P=0.006) and LVM index (-10.0±13.0 g/m2, P=0.006) were documented. Conclusions: The benefit of AVF ligation on LVM and LVM index regression appears to persist long term. This has the potential to lead to a significant reduction in cardiovascular mortality.
Assuntos
Fístula Arteriovenosa , Transplante de Rim , Fístula Arteriovenosa/diagnóstico por imagem , Estudos de Coortes , Seguimentos , Humanos , TransplantadosAssuntos
Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Falência Renal Crônica/complicações , Transplante de Rim , Imageamento por Ressonância Magnética/métodos , Idoso , Feminino , Humanos , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-IdadeRESUMO
Porous biodegradable scaffolds have many applications in bioengineering, ranging from cell culture and transplantation, to support structures, to induce blood vessel and tissue formation in vivo. While numerous strategies have been developed for the manufacture of porous scaffolds, it remains challenging to control the spatial organization of the pores. In this study, we introduce the use of the granular convection effect, also known as the muesli or brazil nut effect, to rapidly engineer particulate templates with a vertical size gradient. These templates can then be used to prepare scaffolds with pore size gradients. To demonstrate this approach, we prepared templates with particle size gradients, which were then infused with a prepolymer solution consisting of the pentaerythritol ethoxylate (polyol), sebacoyl chloride (acid chloride), and poly(caprolactone). Following curing, the template was dissolved to yield biodegradable polyester-ether scaffolds with pore size gradients that could be tuned depending on the size range of the particulates used. The application of these scaffolds was demonstrated using pancreatic islets, which were loaded via centrifugation and retained within the scaffold's pores without a decrease in viability. The proposed strategy provides a facile approach to prepare templates with spatially organized pores that could potentially be used for cell transplantation, or guided tissue formation.
Assuntos
Esferoides Celulares , Engenharia Tecidual/métodos , Alicerces Teciduais , Implantes Absorvíveis , Animais , Cápsulas , Linhagem Celular , Sobrevivência Celular , Transplante de Células/métodos , Regeneração Tecidual Guiada , Humanos , Ilhotas Pancreáticas/citologia , Teste de Materiais , Tamanho da Partícula , Poliésteres , Polímeros , PorosidadeRESUMO
Human bone marrow (BM) derived mesenchymal stem cells (MSC) have high capacity to propagate ex vivo with superior reparative, immunosuppressive, and anti-inflammatory properties. Here we describe standardized protocols and culture conditions that enable the isolation, expansion and maintenance of a highly purified and homogenous population of human MSC. These third party-derived off-the-shelf MSC from healthy human bone marrow donors can potently inhibit mitogenically or allogeneically activated human T cells in proliferation assays. The standard operating procedures described in this chapter can be applied to researchers aiming to enhance MSC immunosuppressive properties and defining MSC mechanisms of action. Importantly, these assays can be incorporated into clinical protocols where the safety and efficacy of human BM MSC can be verified in diseases that are modulated by T cell responses.
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Células da Medula Óssea/imunologia , Medula Óssea/imunologia , Células-Tronco/imunologia , Adulto , Proliferação de Células/fisiologia , Células Cultivadas , Feminino , Humanos , Ativação Linfocitária/imunologia , Masculino , Células-Tronco Mesenquimais/imunologia , Linfócitos T/imunologia , Adulto JovemRESUMO
Kidney transplantation restores fertility in patients with end-stage renal disease, with many successful pregnancies after kidney transplantation being reported. However, there are little data regarding pregnancy in women transplanted under modern-era desensitisation protocols that utilise rituximab, plasma exchange and intravenous immunoglobulin, including ABO-incompatible transplants. Pregnancies in ABO-incompatible recipients can pose new challenges from an immunological perspective. Here, we report a case of successful pregnancy using in vitro fertilisation, in a renal transplant recipient who underwent desensitisation two years prior, that included use of rituximab and plasma exchange to receive an ABO-incompatible transplant from her husband and subsequent father of the baby. We believe this was the first case of successful pregnancy after ABO-incompatible kidney transplantation in Australia and New Zealand. This case also highlights the difficulties faced in conception following transplantation and demonstrates that in vitro fertilisation utilising ovulation induction can be successfully utilised for conception in this cohort. This recipient also had gestational diabetes, worsening renal function and preterm delivery which are important complications often seen in pregnancies of solid organ transplant recipients.
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The field of regenerative medicine provides enormous opportunities for generating beta cells from different stem cell sources for cellular therapy. Even though insulin-secreting cells can be generated from a variety of stem cell types like pluripotent stem cells and embryonic stem cells, the ideal functional cells should be generated from patients' own cells and expanded to considerable levels by non-integrative culture techniques. In terms of the ease of isolation, plasticity, and clinical translation to generate autologous cells, mesenchymal stem cell stands superior. Furthermore, small molecules offer a great advantage in terms of generating functional beta cells from stem cells. Research suggests that most of the mesenchymal stem cell-based protocols to generate pancreatic beta cells have small molecules in their cocktail. However, most of the protocols generate cells that mimic the characteristics of human beta cells, thereby generating "beta cell-like cells" as opposed to mature beta cells. Diabetic therapy becomes feasible only when there are robust, functional, and safe cells for replacing the damaged or lost beta cells. In this review, we discuss the current protocols used to generate beta cells from mesenchymal cells, with emphasis on small molecule-mediated conversion into insulin-producing beta cell-like cells. Our data and the data presented from the references within this review would suggest that although mesenchymal stem cells are an attractive cell type for cell therapy they are not readily converted into functional mature beta cells.
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Técnicas de Reprogramação Celular/métodos , Diabetes Mellitus/terapia , Células Secretoras de Insulina/citologia , Células-Tronco Mesenquimais/citologia , Animais , Transplante de Células/métodos , Humanos , Células Secretoras de Insulina/transplanteRESUMO
BACKGROUND: Cardiovascular disease is the leading cause of death in patients with chronic kidney disease. Studies investigating the disproportionate burden of cardiovascular disease have occurred predominantly in the peripheral vasculature, often used noninvasive imaging modalities, and infrequently recruited patients receiving dialysis. This study sought to evaluate invasive coronary dynamic vascular function in patients with end-stage renal failure (ESRF). PATIENTS AND METHODS: Patients referred for invasive coronary angiography prior to renal transplantation were invited to participate. Control patients were recruited in parallel. Baseline characteristics were obtained. Coronary diameter (via quantitative coronary angiography) and coronary blood flow (via Doppler Flowire) were measured; macrovascular endothelial-dependent and independent effects were evaluated in response to intracoronary acetylcholine infusion (10 and 10 mol/l) and intracoronary glyceryl trinitrate, respectively. Microvascular function was evaluated by response to adenosine and expressed as coronary flow velocity reserve. Mean values were compared. RESULTS: Thirty patients were evaluated: 15 patients with ESRF (mean age 52.1 ± 9, male 73%) and 15 control patients (mean age 53.3 ± 13, male 60%). Comorbidity profile, aside from ESRF, was well matched. Baseline coronary blood flow was similar between groups (101.6 ± 10.3 vs. 103.4 ± 9.1 ml/min, P = 0.71), as was endothelial-dependent response to acetylcholine (159.1 ± 16.9 vs. 171.1 ± 16.8 ml/min, P = 0.41). Endothelial-independent response to glyceryl trinitrate was no different between groups (14.3 ± 3.1 vs. 13.1 ± 2.3%, P = 0.73. A significantly reduced coronary flow velocity reserve was observed in the ESRF cohort compared to controls (2.34 ± 0.4 vs. 3.05 ± 0.3, P = 0.003). CONCLUSION: Patients with ESRF had preserved endothelial-dependent function however compared to controls, demonstrated significantly attenuated microvascular reserve. An impaired response to adenosine may not only represent a component of the pathophysiological milieu in patients with ESRF but may also provide a basis for the suboptimal diagnostic performance of vasodilatory stress in this population.