Pancreas, Islet and Stem Cell Transplantation for Diabetes, 2010
... secretions. Of interest, in a review of 75 consecutive recipients of bladder-drained SPKT, Ke... more ... secretions. Of interest, in a review of 75 consecutive recipients of bladder-drained SPKT, Ketel et al.[9] reported the need to treat metabolic acidosis in 51 patients (76%), 40% of whom had concomitant hyperkalaemia (K+: 6 meq/litre). ...
Acute and chronic kidney injury following orthotopic liver transplantation (OLT) is associated wi... more Acute and chronic kidney injury following orthotopic liver transplantation (OLT) is associated with increased morbidity and mortality. With the increasing longevity of liver transplant recipients, chronic kidney disease (CKD) has become an increasingly prevalent complication among long-term survivors. This article provides an overview of the literature on suggested risk factors for acute and CKD following OLT and a discussion of an approach to their medical management. In OLT candidates with pretransplant renal dysfunction, the use of interleukin-2 receptor blockers or antithymocyte globulin induction therapy in conjunction with delayed introduction of calcineurin inhibitors may preserve early renal function. In long-term stable OLT recipients with established calcineurin inhibitor nephrotoxicity, calcineurin inhibitor minimization or withdrawal protocols may halt or ameliorate renal dysfunction without compromising patient and graft survival. However, large-scale, multicenter, randomized controlled trials are still needed. The occurrence of acute kidney injury is common immediately after OLT, whereas the incidence of CKD and end-stage renal disease increases with time. Identifying patients at risk for acute kidney injury and CKD following OLT and early implementation of measures to preserve, halt, or ameliorate the progression of renal dysfunction should be an integral part in the management of OLT recipients.
Kidney Transplantation: A Guide to the Care of Kidney Transplant Recipients, 2010
Early post-transplant factors including delayed graft function (DGF), acute rejection episodes, n... more Early post-transplant factors including delayed graft function (DGF), acute rejection episodes, nephrotoxic agents, post-transplant hypertension, dyslipidemia, and new onset diabetes mellitus after transplantation (NODAT) have all been implicated in worsening both short- and long-term morbidity and mortality after renal transplantation. Optimal management of the transplant recipient begins in the immediate postoperative period. This chapter provides a stepwise approach to the
Kidney Transplantation: A Guide to the Care of Kidney Transplant Recipients, 2010
Renal transplantation is the treatment modality of choice for virtually all suitable candidates w... more Renal transplantation is the treatment modality of choice for virtually all suitable candidates with end-stage renal disease. Compared to dialysis, kidney transplantation improves both patient survival and quality of life. Studies suggest that the survival advantage of ...
Kidney Transplantation: A Guide to the Care of Kidney Transplant Recipients, 2010
New onset diabetes mellitus after transplantation (NODAT) is a serious and frequently observed co... more New onset diabetes mellitus after transplantation (NODAT) is a serious and frequently observed complication following solid organ transplantation. Kidney transplant recipients who develop NODAT are at increased risk of fatal and non-fatal cardiovascular events and other adverse outcomes including infection, reduced patient survival, graft rejection, and accelerated graft loss compared with those who do not develop diabetes. Identification of high-risk
The advent of potent antiplatelet and antithrombotic agents over the past decade has resulted in ... more The advent of potent antiplatelet and antithrombotic agents over the past decade has resulted in significant improvement in reducing ischemic events in acute coronary syndrome (ACS). However, the use of antiplatelet and antithrombotic combination therapy, often in the settings of percutaneous coronary intervention (PCI), has led to an increase in the risk of bleeding. In patients with non-ST elevation myocardial infarction treated with antithrombotic agents, bleeding has been reported to occur in 0.4%-10% of patients, whereas in patients undergoing PCI, periprocedural bleeding occurs in 2.2%-14% of cases. Until recently, bleeding was considered an intrinsic risk of antithrombotic therapy, and efforts to reduce bleeding have received little attention. There have been increasing data demonstrating that bleeding is associated with adverse outcomes, including myocardial infarction, stroke, and death. Therefore, it is imperative to optimize patient outcomes by adopting pharmacological and nonpharmacological strategies to minimize bleeding while maximizing treatment efficacy. In this paper, we present a review of the bleeding classifications used in large-scale clinical trials in patients with ACS and those undergoing PCI treated with antiplatelets and antithrombotic agents, adverse outcomes, particularly mortality associated with bleeding complications, and suggested predictive risk factors. Potential mechanisms of the association between bleeding and mortality and strategies to reduce bleeding complications are also discussed.
Pulmonary toxicity has recently been recognized as a potentially serious complication associated ... more Pulmonary toxicity has recently been recognized as a potentially serious complication associated with sirolimus therapy. We further detail this condition on the basis of our own cases and those reported in the literature. We report three cases of suspected sirolimus-induced pulmonary toxicity that occurred in three renal transplant recipients and searched PubMed for all previously reported cases. Including our current cases, 43 patients with sirolimus-induced pulmonary toxicity have now been reported. Clinical data were incomplete in 28 cases. Analysis of available data for 15 patients revealed that the most commonly presenting symptoms were dyspnea on exertion and dry cough followed by fatigue and fever. Chest radiographs and high-resolution computed tomography scans commonly revealed bilateral patchy or diffuse alveolo-interstitial infiltrates. Bronchoalveolar fluid analysis and lung biopsy in selected case reports revealed several distinct histologic features, including lymphocytic alveolitis, lymphocytic interstitial pneumonitis, bronchoalveolar obliterans organizing pneumonia, focal fibrosis, pulmonary alveolar hemorrhage, or a combination thereof. The diagnosis of sirolimus-associated pulmonary toxicity was made after an exhaustive work-up to exclude infectious causes and other pulmonary disease. Sirolimus discontinuation or dose reduction resulted in clinical and radiologic improvement in all 15 patients within 3 weeks. The temporal relationship between sirolimus exposure and onset of pulmonary symptoms in the absence of infectious causes and other alternative pulmonary disease and the associated clinical and radiologic improvement after its cessation suggests a causal relationship. Because the use of sirolimus in organ transplantation has become more widespread, clinicians must remain vigilant to its potential pulmonary complication.
Over the past decade, patients returning to dialysis after a failed transplant comprised of 5-10%... more Over the past decade, patients returning to dialysis after a failed transplant comprised of 5-10% of the annual number of dialysis initiations in the United States, whereas retransplant candidates account for 5.0-13% of the annual deceased donor wait-list additions. The United States Renal Data System (USRDS) database revealed a >3-fold increase in the annual adjusted death rates for patients returning to dialysis after graft loss compared with patients with a functioning allograft (9.4% vs. 2.8%, respectively). Continuation of low-dose immunosuppression to maintain residual allograft function has been suggested as a contributing factor, presumably via treatment-related infectious and cardiovascular complications among others. In contrast, a
The prevalence of obesity (body mass index ≥30 kg/m(2)) at the time of transplantation among kidn... more The prevalence of obesity (body mass index ≥30 kg/m(2)) at the time of transplantation among kidney transplant recipients in the United States has doubled between 1987 and 2001 and continues to increase inexorably. Single-center and large registry studies in kidney transplant recipients demonstrated that high body mass index (BMI) at transplant is associated with increased risk of wound and surgical site infections, delayed graft function (DGF), acute rejection episodes, and graft loss, among others. Hence, in many centers, obese transplant candidates are denied a transplant based on their body mass index (BMI) alone. The impact of obesity on short- and long-term graft and patient outcomes after kidney transplantation are herein revisited, followed by the authors' proposed approach to evaluate and select obese transplant candidates for a kidney transplant. Suggested interventions to optimize the health of such candidates are also discussed.
This Practice Point commentary discusses the findings of a prospective study by Kuypers et al. th... more This Practice Point commentary discusses the findings of a prospective study by Kuypers et al. that was designed to determine the best clinical diagnostic tool for identifying patients at risk of developing post-transplantation diabetes mellitus (PTDM) following renal ...
Acute renal failure (ARF) is common immediately after orthotopic liver transplantation (OLT), whe... more Acute renal failure (ARF) is common immediately after orthotopic liver transplantation (OLT), whereas the incidences of chronic kidney disease (CKD) and end-stage renal disease increase with time. Introduction of the Model for End-stage Liver Disease (MELD) score-intended to prioritize patients with more-severe pretransplantation liver disease in general, and worse pretransplantation renal function in particular-for the allocation of liver grafts led to concerns about compromised patient and allograft survival and increased incidence of postoperative ARF and CKD. Nonetheless, it has been suggested that early OLT of candidates with baseline renal dysfunction improves post-transplantation renal outcomes. For OLT candidates with mild to moderate chronic renal impairment or recent-onset ARF, the decision of whether to perform OLT alone or combined liver-kidney transplantation (CLKT) can be challenging because no single factor has been shown to be predictive of the degree of renal function recovery or CKD progression following successful OLT. In this article, we provide an overview of the literature on renal function outcomes following OLT and CLKT, share our perspectives on the potential predictors of renal dysfunction or nonrecovery of renal function after OLT, and present United Network for Organ Sharing data on patient and allograft outcomes in CLKT recipients in the pre-MELD and post-MELD eras. Mechanisms that might underlie immunological protection of kidney grafts by liver allografts are also discussed.
Pancreas, Islet and Stem Cell Transplantation for Diabetes, 2010
... secretions. Of interest, in a review of 75 consecutive recipients of bladder-drained SPKT, Ke... more ... secretions. Of interest, in a review of 75 consecutive recipients of bladder-drained SPKT, Ketel et al.[9] reported the need to treat metabolic acidosis in 51 patients (76%), 40% of whom had concomitant hyperkalaemia (K+: 6 meq/litre). ...
Acute and chronic kidney injury following orthotopic liver transplantation (OLT) is associated wi... more Acute and chronic kidney injury following orthotopic liver transplantation (OLT) is associated with increased morbidity and mortality. With the increasing longevity of liver transplant recipients, chronic kidney disease (CKD) has become an increasingly prevalent complication among long-term survivors. This article provides an overview of the literature on suggested risk factors for acute and CKD following OLT and a discussion of an approach to their medical management. In OLT candidates with pretransplant renal dysfunction, the use of interleukin-2 receptor blockers or antithymocyte globulin induction therapy in conjunction with delayed introduction of calcineurin inhibitors may preserve early renal function. In long-term stable OLT recipients with established calcineurin inhibitor nephrotoxicity, calcineurin inhibitor minimization or withdrawal protocols may halt or ameliorate renal dysfunction without compromising patient and graft survival. However, large-scale, multicenter, randomized controlled trials are still needed. The occurrence of acute kidney injury is common immediately after OLT, whereas the incidence of CKD and end-stage renal disease increases with time. Identifying patients at risk for acute kidney injury and CKD following OLT and early implementation of measures to preserve, halt, or ameliorate the progression of renal dysfunction should be an integral part in the management of OLT recipients.
Kidney Transplantation: A Guide to the Care of Kidney Transplant Recipients, 2010
Early post-transplant factors including delayed graft function (DGF), acute rejection episodes, n... more Early post-transplant factors including delayed graft function (DGF), acute rejection episodes, nephrotoxic agents, post-transplant hypertension, dyslipidemia, and new onset diabetes mellitus after transplantation (NODAT) have all been implicated in worsening both short- and long-term morbidity and mortality after renal transplantation. Optimal management of the transplant recipient begins in the immediate postoperative period. This chapter provides a stepwise approach to the
Kidney Transplantation: A Guide to the Care of Kidney Transplant Recipients, 2010
Renal transplantation is the treatment modality of choice for virtually all suitable candidates w... more Renal transplantation is the treatment modality of choice for virtually all suitable candidates with end-stage renal disease. Compared to dialysis, kidney transplantation improves both patient survival and quality of life. Studies suggest that the survival advantage of ...
Kidney Transplantation: A Guide to the Care of Kidney Transplant Recipients, 2010
New onset diabetes mellitus after transplantation (NODAT) is a serious and frequently observed co... more New onset diabetes mellitus after transplantation (NODAT) is a serious and frequently observed complication following solid organ transplantation. Kidney transplant recipients who develop NODAT are at increased risk of fatal and non-fatal cardiovascular events and other adverse outcomes including infection, reduced patient survival, graft rejection, and accelerated graft loss compared with those who do not develop diabetes. Identification of high-risk
The advent of potent antiplatelet and antithrombotic agents over the past decade has resulted in ... more The advent of potent antiplatelet and antithrombotic agents over the past decade has resulted in significant improvement in reducing ischemic events in acute coronary syndrome (ACS). However, the use of antiplatelet and antithrombotic combination therapy, often in the settings of percutaneous coronary intervention (PCI), has led to an increase in the risk of bleeding. In patients with non-ST elevation myocardial infarction treated with antithrombotic agents, bleeding has been reported to occur in 0.4%-10% of patients, whereas in patients undergoing PCI, periprocedural bleeding occurs in 2.2%-14% of cases. Until recently, bleeding was considered an intrinsic risk of antithrombotic therapy, and efforts to reduce bleeding have received little attention. There have been increasing data demonstrating that bleeding is associated with adverse outcomes, including myocardial infarction, stroke, and death. Therefore, it is imperative to optimize patient outcomes by adopting pharmacological and nonpharmacological strategies to minimize bleeding while maximizing treatment efficacy. In this paper, we present a review of the bleeding classifications used in large-scale clinical trials in patients with ACS and those undergoing PCI treated with antiplatelets and antithrombotic agents, adverse outcomes, particularly mortality associated with bleeding complications, and suggested predictive risk factors. Potential mechanisms of the association between bleeding and mortality and strategies to reduce bleeding complications are also discussed.
Pulmonary toxicity has recently been recognized as a potentially serious complication associated ... more Pulmonary toxicity has recently been recognized as a potentially serious complication associated with sirolimus therapy. We further detail this condition on the basis of our own cases and those reported in the literature. We report three cases of suspected sirolimus-induced pulmonary toxicity that occurred in three renal transplant recipients and searched PubMed for all previously reported cases. Including our current cases, 43 patients with sirolimus-induced pulmonary toxicity have now been reported. Clinical data were incomplete in 28 cases. Analysis of available data for 15 patients revealed that the most commonly presenting symptoms were dyspnea on exertion and dry cough followed by fatigue and fever. Chest radiographs and high-resolution computed tomography scans commonly revealed bilateral patchy or diffuse alveolo-interstitial infiltrates. Bronchoalveolar fluid analysis and lung biopsy in selected case reports revealed several distinct histologic features, including lymphocytic alveolitis, lymphocytic interstitial pneumonitis, bronchoalveolar obliterans organizing pneumonia, focal fibrosis, pulmonary alveolar hemorrhage, or a combination thereof. The diagnosis of sirolimus-associated pulmonary toxicity was made after an exhaustive work-up to exclude infectious causes and other pulmonary disease. Sirolimus discontinuation or dose reduction resulted in clinical and radiologic improvement in all 15 patients within 3 weeks. The temporal relationship between sirolimus exposure and onset of pulmonary symptoms in the absence of infectious causes and other alternative pulmonary disease and the associated clinical and radiologic improvement after its cessation suggests a causal relationship. Because the use of sirolimus in organ transplantation has become more widespread, clinicians must remain vigilant to its potential pulmonary complication.
Over the past decade, patients returning to dialysis after a failed transplant comprised of 5-10%... more Over the past decade, patients returning to dialysis after a failed transplant comprised of 5-10% of the annual number of dialysis initiations in the United States, whereas retransplant candidates account for 5.0-13% of the annual deceased donor wait-list additions. The United States Renal Data System (USRDS) database revealed a >3-fold increase in the annual adjusted death rates for patients returning to dialysis after graft loss compared with patients with a functioning allograft (9.4% vs. 2.8%, respectively). Continuation of low-dose immunosuppression to maintain residual allograft function has been suggested as a contributing factor, presumably via treatment-related infectious and cardiovascular complications among others. In contrast, a
The prevalence of obesity (body mass index ≥30 kg/m(2)) at the time of transplantation among kidn... more The prevalence of obesity (body mass index ≥30 kg/m(2)) at the time of transplantation among kidney transplant recipients in the United States has doubled between 1987 and 2001 and continues to increase inexorably. Single-center and large registry studies in kidney transplant recipients demonstrated that high body mass index (BMI) at transplant is associated with increased risk of wound and surgical site infections, delayed graft function (DGF), acute rejection episodes, and graft loss, among others. Hence, in many centers, obese transplant candidates are denied a transplant based on their body mass index (BMI) alone. The impact of obesity on short- and long-term graft and patient outcomes after kidney transplantation are herein revisited, followed by the authors' proposed approach to evaluate and select obese transplant candidates for a kidney transplant. Suggested interventions to optimize the health of such candidates are also discussed.
This Practice Point commentary discusses the findings of a prospective study by Kuypers et al. th... more This Practice Point commentary discusses the findings of a prospective study by Kuypers et al. that was designed to determine the best clinical diagnostic tool for identifying patients at risk of developing post-transplantation diabetes mellitus (PTDM) following renal ...
Acute renal failure (ARF) is common immediately after orthotopic liver transplantation (OLT), whe... more Acute renal failure (ARF) is common immediately after orthotopic liver transplantation (OLT), whereas the incidences of chronic kidney disease (CKD) and end-stage renal disease increase with time. Introduction of the Model for End-stage Liver Disease (MELD) score-intended to prioritize patients with more-severe pretransplantation liver disease in general, and worse pretransplantation renal function in particular-for the allocation of liver grafts led to concerns about compromised patient and allograft survival and increased incidence of postoperative ARF and CKD. Nonetheless, it has been suggested that early OLT of candidates with baseline renal dysfunction improves post-transplantation renal outcomes. For OLT candidates with mild to moderate chronic renal impairment or recent-onset ARF, the decision of whether to perform OLT alone or combined liver-kidney transplantation (CLKT) can be challenging because no single factor has been shown to be predictive of the degree of renal function recovery or CKD progression following successful OLT. In this article, we provide an overview of the literature on renal function outcomes following OLT and CLKT, share our perspectives on the potential predictors of renal dysfunction or nonrecovery of renal function after OLT, and present United Network for Organ Sharing data on patient and allograft outcomes in CLKT recipients in the pre-MELD and post-MELD eras. Mechanisms that might underlie immunological protection of kidney grafts by liver allografts are also discussed.
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