Safety and effectiveness of percutaneous embolization for late failed renal allograft in patients with graft intolerance syndrome.

OBJECTIVE: To investigate the clinical safety and effectiveness of percutaneous embolization in treating the late failed renal allograft in patients with graft intolerance syndrome (GIS). METHODS: Transcatheter embolization of renal graft artery was performed in 18 patients with late graft dysfunction and GIS. The subsequent complications, postoperative symptom remission rate, and prognosis were assessed. RESULTS: GIS was relieved in 15 patients (83.3%), of which 6 patients (33.3%) had severer fever and pain in the area of renal graft after embolization, which lasted for a mean of 3.5 days (range: 2-5 days). GIS persisted for more than 2 weeks in 3 patients (16.7%), who ultimately underwent surgical removal of grafts. No severe embolism-associated complications were noted. CONCLUSION: Percutaneous embolization can effectively avoid surgical graft removal in patients with late renal allograft failure, and therefore can be used as a safe and effective treatment for the late failed renal allograft combined with GIS.

Intractable ascites without mechanical vascular obstruction after orthotopic liver transplantation: etiology and clinical outcome of sinusoidal obstruction syndrome.

Intractable ascites after orthotopic liver transplantation (OLT) is a relatively rare complication. However, it often takes a life threatening course, which requires re-transplantation. In previous studies, several reports gave hepatic sinusoidal obstruction syndrome (SOS) as one of the causes of refractory ascites. However, the detailed etiology of SOS after OLT and its association with clinical consequences remain unclear because there have been few studies to date. We report two recent cases with rapidly progressive refractory ascites associated with SOS, following completely different clinical courses. In case 1, the first episode of acute allograft rejection triggered SOS and subsequent intractable ascites, while the second acute rejection worsened his clinical status. A transjugular intrahepatic portosystemic stent-shunt (TIPS) was placed and this procedure resulted in complete disappearance of ascites and of renal dysfunction. In contrast, refractory ascites in case 2, who had neither rejection nor mechanical outlet obstruction, worsened despite TIPS stent placement, and re-transplantation was necessary. We speculate that the pre-existing diseased liver of the cadaver donor caused this serious complication, necessitating a second graft.

Clinical Course, Imaging Features, and Outcomes of COVID-19 in Kidney Transplant Recipients.

Coronavirus disease 2019 (COVID-19) is a novel and highly contagious disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Older adults and patients with comorbidities and immunosuppressive conditions may experience severe signs and symptoms that can lead to death. This case series assesses the clinical course, imaging features, and outcomes for 12 patients with COVID-19 and a history of kidney transplantation. Patients were evaluated for symptoms, laboratory data, imaging findings, and outcomes from February 2020 to April 2020. Fever, cough, and dyspnea were the most common clinical symptoms, noted in 75% (nine/12), 75% (nine/12), and 41.7% (five/12) of the patients, respectively. Most of the patients had a normal white blood cell count, while 33.3% (four/12) had leukopenia and 8.3% (one/12) had leukocytosis. A combination of consolidation and ground glass opacity was the most predominant (75%) pattern of lung involvement on computed tomography (CT). Eight patients died of severe COVID-19 pneumonia and acute respiratory distress syndrome and four were discharged. All recovered cases had a unilateral peripheral pattern of involvement limited to only one zone on initial chest CT. It seems that CT imaging has an important role in predicting COVID-19 outcomes for solid organ transplant recipients. Future studies with long-term follow up and more cases are needed to elucidate COVID-19 diagnosis, outcome, and management strategies for these patients.

Treatment of Posttransplantation Anemia.

Kidney transplantation represents a renal replacement therapy for end-stage renal failure, with outcomes improving from year to year. With the improved survival prognosis, treatment of complications of chronic kidney disease after transplantation is becoming increasingly important. In particular, posttransplantation anemia (PTA) is often protracted, which could be related to a variety of factors, including the renal function status, graft rejection episodes, and infectious causes. PTA occurs in about 30-40% of transplant recipients, and is known to affect the function of the transplanted kidney as well as patient survival. Early PTA is associated with a risk of death and cardiovascular disorders, however, during this phase, priority is given to the appropriate maintenance of immunosuppression rather than to the treatment of anemia. Maintenance-phase PTA exerts a strong influence on the survival, prognosis of the transplanted kidney, quality of life, etc. Unlike the disease state and treatment of usual renal anemia, it has been suggested that PTA may possibly reflect the functional state of the transplanted kidney. Therefore, it has been suggested that proper renal function may be maintained by ensuring a normal hemoglobin level in kidney transplant recipients. Proper management of PTA could be expected to be associated with an improved prognosis of the transplanted kidney and improved patient survival in kidney transplant recipients. It is advisable to provide appropriate treatment by setting target levels in accordance with the dialysis vintage, primary disease, cardiovascular complications, and kidney transplant function and delineation of the transplant recipient characteristics.

Acute Cellular Rejection in ABO-Incompatible Renal Transplant Recipients Receiving Rituximab Is Associated with Delayed-Onset Neutropenia.

BACKGROUND Rituximab induces long-lasting B cell depletion in the peripheral blood and increases the levels of proinflammatory cytokines associated with regulatory B cell depletion. Previous reports showed that B cell-related cytokine release after administration of rituximab may induce acute cellular rejection (ACR) and delayed-onset neutropenia. The present study was conducted to investigate the correlation between acute rejection and delayed-onset neutropenia in ABO-incompatible renal transplant recipients who underwent administration of rituximab for 1 year after transplantation. MATERIAL AND METHODS From June 2006 to July 2015, 47 patients with chronic renal failure received ABO-incompatible renal transplant with rituximab induction at Osaka City University Hospital. All 47 patients underwent plasmapheresis due to removal of anti-A/B antibodies and administration of rituximab, and their transplants were carried out successfully. We investigated the correlation between ACR and delayed-onset neutropenia in ABO-incompatible renal transplant recipients who underwent administration of rituximab for 1 year after transplantation. RESULTS Fourteen patients (29.8%) experienced ACR (group A), and 33 recipients did not develop ACR (group B). The frequency of delayed-onset neutropenia was higher in group A than in group B (p=0.0503). Multivariate logistic regression analysis revealed that the frequency of ACR correlated significantly with the prevalence of delayed-onset neutropenia. CONCLUSIONS Our results indicated that ACR in ABO-incompatible renal transplant recipients receiving rituximab was associated with delayed-onset neutropenia.

Efficacy of Eculizumab Therapy for Atypical Hemolytic Uremic Syndrome Recurrence and Antibody-Mediated Rejection Progress After Renal Transplantation With Preformed Donor-Specific Antibodies: Case Report.

Atypical hemolytic uremic syndrome (aHUS) develops as the result of unregulated complement progression and precipitates de novo thrombotic microangiopathy. Plasma therapy is used to control the progression of the complement cascade, but that therapy is not effective in all patients and is accompanied by risk of infection and/or allergy. Eculizumab has been reported as an efficient therapy for aHUS. We report the case of a 35-year old woman who underwent effective eculizumab therapy for aHUS recurrence and antibody-mediated rejection (AMR) progress after renal transplantation with preformed donor-specific antibodies (DSA). She developed end-stage renal disease due to suspicious IgA nephropathy at age 33 years. Kidney transplantation was performed at age 35 years, and aHUS recurred 2 weeks later, leading to the progressive hemolytic anemia and renal dysfunction. Therefore, she underwent plasma therapy several times. Because it was difficult to continue to plasma therapy for severe allergy, eculizumab was proposed as an alternate therapy. Treatment with eculizumab was initiated 36 days after renal transplantation. After 3 years of eculizumab treatment, and without plasma therapy, schistocytes decreased, haptoglobin increased to within normal limits, creatinine levels stabilized, and no further episodes of diarrhea were reported. At protocol biopsy 1 year after transplantation, she was diagnosed with C4d-negative subclinical AMR. However, her pathologic findings at follow-up biopsy 3 years after transplantation were recovered. We conclude that eculizumab alone, without plasma therapy, is sufficient to treat recurrence of aHUS and AMR due to DSA after renal transplantation and to maintain long-term graft function.

The Bad and the Good News on Cancer Immunotherapy: Implications for Organ Transplant Recipients.

Cancer immunotherapy, especially the use of checkpoint inhibitors, is expanding and can be efficacious in organ transplant recipients with malignant neoplasia. In this review, we summarize clinical findings and evolution of several patients treated with CTL4-4 or PD-1 inhibitors reported in the literature. The CTL-4 inhibitor ipilimumab has been safely used in several liver and kidney allograft recipients. PD1-inhibitors look promising for tumor shrinking, but acute rejection is the rule, so they should be avoided in recipients of life-saving organs. Immunosuppression minimization, especially calcineurin inhibitor withdrawal is needed for adequate responses to checkpoint inhibitor treatments. The addition of sirolimus or everolimus may be helpful for mitigation rejections. The future will tell if selective boost of cancer-specific T-cell repertoire, possibly with the help of anticancer vaccines or adoptive T-cell transfer, will improve outcomes and decrease undesirable events.

Successful Orthotopic Heart Transplantation and Immunosuppressive Management in 2 Human Immunodeficiency Virus-Seropositive Patients.

Few orthotopic heart transplantations have been performed in patients infected with the human immunodeficiency virus since the first such case was reported in 2001. Since that time, advances in highly active antiretroviral therapy have resulted in potent and durable suppression of the causative human immunodeficiency virus-accompanied by robust immune reconstitution, reversal of previous immunodeficiency, a marked decrease in opportunistic and other infections, and near-normal long-term survival. Although human immunodeficiency virus infection is not an absolute contraindication, few centers in the United States and Canada have performed heart transplantations in this patient population; these patients have been de facto excluded from this procedure in North America. Re-evaluation of the reasons for excluding these patients from cardiac transplantation is warranted in light of such significant advances in antiretroviral therapy. This case report documents successful orthotopic heart transplantation in 2 patients infected with human immunodeficiency virus, and we describe their antiretroviral therapy and immunosuppressive management challenges. Both patients were doing well without sequelae 43 and 38 months after transplantation.

A multicenter, prospective study of C2-monitored cyclosporine microemulsion in a U.S. population of de novo renal transplant recipients.

BACKGROUND: Monitoring cyclosporine microemulsion (CsA-ME; Neoral) exposure 2 hours postdose (C2) has been reported to optimize the efficacy and safety of CsA-ME therapy. The addition of induction therapy to a maintenance regimen including CsA-ME C2 monitoring has not been evaluated. METHODS: In all, 123 adult renal transplant recipients were recruited at 14 U.S. centers for this 6-month study. CsA-ME dose was to be titrated to attain C2 targets of 1700 and 1500 ng/ml during posttransplant months 1 and 2, respectively. After 2 months, patients were randomized to one of two groups with different, decreasing C2 targets. Basiliximab, mycophenolate mofetil, and corticosteroids completed the study immunosuppression. RESULTS: Of the 119 evaluable patients, 76% were male, 22% African American, and 66% deceased donor recipients. Biopsy-proven acute rejection occurred in 10 patients (9.3%); there were two failed grafts and one death. Serum creatinine and calculated GFR values suggest good renal function, with month 6 medians of 1.5 ng/ml and 67 ml/min/1.73 m. Safety and tolerability assessments revealed no unexpected outcomes. Observed C2 levels were generally lower than protocol targets, particularly in the first weeks posttransplantation. CONCLUSIONS: The striking efficacy and outcomes may have been achieved in this study with lower C2 levels of CsA-ME because of the addition of basiliximab induction.

Importance of concomitant viral infection during late acute liver allograft rejection.

We have determined accompanying events and reviewed the management and outcome of late acute cellular rejection episodes in 384 consecutive liver recipients. A significant proportion of patients experienced concomitant viral infection (group 1, n = 15 [41%]), with CMV infection comprising the largest group and smaller contributions from other viruses (CMV, 30%; HSV, 5%; EBV, 3%; varicella zoster virus, 3%). Thirteen (35%) patients (group 2) developed late rejection associated with low maintenance immunosuppression, and in a further 10 patients (group 3), no accompanying factor could be identified. Refractory rejection was higher in late compared with early rejection episodes in our series (29% vs. 9.2%, P < 0.05). Antiviral chemotherapy administered in rejection episodes with concomitant viral infection, either as sole treatment in cases with accompanying hepatitis or as adjunctive therapy to further supplemental immunosuppression in episodes of steroid-resistant rejection, controlled the rejection process in all treated patients.

Fever in dialysis patients with recently rejected renal allografts.

INTRODUCTION: Fever of unknown origin is a complex problem in dialysis patients with recently rejected renal allografts, due to the contribution of the newly withheld immunosuppressive agents to the immunosuppression of uremia, resulting in an atypical presentation of infections, a main cause of fever in these cases. MATERIALS AND METHODS: Two dialysis patients with recently rejected renal allografts who were hospitalized because of fever of unknown origin are reported. Biochemical, bacteriological and imaging studies were performed for specific diagnosis. RESULTS: Extensive laboratory investigations failed to yield any diagnosis and allograft nephrectomy was performed in one patient, with a probable diagnosis of inflammation of the allograft, which resulted in no improvement. Eventually, both patients were found to have adrenal insufficiency responsible for the fever, which improved after steroid replacement. CONCLUSIONS: Adrenal insufficiency should be suspected in all dialysis patients presenting with fever and atypical symptoms, but only after other potential causes are eliminated; since steroid administration may normalize fever regardless of the etiology, it may mask the signs and symptoms and delay the treatment of other (if any) underlying disorder(s).

[Extrasystole following heart transplantation]. / Extrasystolie nach Herztransplantation.

A 43 year old man developed extensive supraventricular and ventricular extrasystoles (over 500 supraventricular extrasystoles per hour, VES class II) within 3 months after orthotopic heart transplantation because of dilatative cardiomyopathy. At the same time severe graft rejection (class III according to Billingham) was documented. After treatment of the rejection the following three controls by 24 hours Holter EKG showed only slight supraventricular extrasystoles of less than 10 per hour and in three consecutive myocardial biopsies no rejection process requiring additional treatment was found. In individual cases severe ventricular arrhythmia registered by the family doctor may be a first hint for early rejection. Since intervals for inpatient controls have been extended observation of extrasystoles may be helpful for initiation of a next inpatient control. Incidence of extrasystoles after heart transplantation in the cyclosporine-era is discussed.

Are we near to an effective drug treatment for bronchiolitis obliterans?

Lung transplantation remains the only effective therapeutic option for well-selected patients with end-stage (cardio) pulmonary diseases such as emphysema, cystic fibrosis, lung fibrosis and pulmonary arterial hypertension. Although the results have improved lately, the long-term survival is still far behind other organ transplantations. This is mainly due to the development of chronic lung allograft dysfunction (CLAD), with bronchiolitis obliterans (BO) being the most frequent manifestation and restrictive CLAD or restrictive allograft syndrome (RAS) being a rather novel distinct entity, with a worse survival. Although the pathology of BO has been well described, this is not an obvious diagnosis after lung transplantation, because of the low sensitivity of transbronchial biopsies to detect BO. As a consequence, BO syndrome (BOS), the clinical correlate of BO, characterized by a progressive and obstructive decline in FEV1, has been introduced and is used worldwide to describe patients affected by this condition. BOS is the major long-term problem after lung transplantation, occurring in some 50% of patients within 5 years after the transplant procedure and causing up to 30% of late mortality between 3 and 5 years after transplantation. Its treatment remains very difficult, although recent advances have certainly improved the survival after diagnosis of BOS. We will here review the current therapeutic options to try to prevent BOS on the one hand and to treat BOS on the other hand.

Skin changes following organ transplantation: an interdisciplinary challenge.

BACKGROUND: The immunosuppressants used in transplantation medicine significantly elevate the incidence of neoplasia, particularly in the skin. The cumulative incidence of non-melanocytic skin cancer (NMSC) in renal transplant recipients was 20.5% in a study carried out in German centers. Data on more than 35 000 renal transplant recipients in the USA document a cumulative NMSC incidence of over 7% after 3 years of immunosuppression. METHOD: The authors selectively review publications obtained by a PubMed search to discuss the incidence of, and major risk factors for, skin tumors and infectious diseases of the skin in immunosuppressed patients. RESULTS: The main risk factors for skin tumors are age at the time of transplantation, light skin color, previous and present exposure to sunlight, and the type and duration of immunosuppressive treatment. Squamous-cell carcinoma (SCC) is the most common kind of skin tumor in immunosuppressed patients. Human herpesvirus 8 and Merkel-cell polyoma virus also cause neoplasia more often in immunosuppressed patients than in the general population. Surgical excision is the treatment of choice. Actinic keratosis markedly elevates the risk that SCC will arise in the same skin area (odds ratio 18.36, 95% confidence interval 3.03-111). Patients with multiple actinic keratoses can be treated with photodynamic therapy or with acitretin. To lower the skin cancer risk, organ transplant recipients should apply medical screening agents with a sun protection factor of at least 50 to exposed skin areas every day. 55% to 97% of organ transplant recipients have skin infections; these are treated according to their respective types. CONCLUSION: Squamous-cell carcinoma of the skin adds to the morbidity and mortality of transplant recipients and is therefore among the major oncological challenges in this patient group. Structured concepts for interdisciplinary care enable risk-adapted treatment.

New options and perspectives for proteinuria management after kidney transplantation.

Proteinuria has been strongly correlated with reduced function and graft survival in kidney-transplanted patients. Data regarding new strategies in proteinuria treatment and subsequent allograft survival are lacking. Similarities between chronic graft injury and chronic kidney disease (CKD) suggest that the same therapeutic antiproteinuric tools should be effective in kidney-transplanted patients. The classic strategies to decrease proteinuria such as blood pressure control, nicotine cessation, low-salt diet, and maintaining an ideal body weight seem to be not enough to achieve proteinuria control. Improvements in our understanding of the pathogenesis of CKD have led to the identification of several novel targets for proteinuria management. In this review, we discuss novel pharmacological approaches that aim to decrease proteinuria in CKD patients, including the use of direct renin inhibitors, vitamin D analogs, pentoxifylline, and endothelin receptor antagonists. We also discuss the promise of using antifibrotic agents to treat proteinuria. The identification of new biomarkers of CKD and its progression can help in the selection of the most effective treatment for decreasing proteinuria and maintaining kidney function.

Management of proteinuria in clinical practice after kidney transplantation.

Proteinuria is a marker of poor prognosis in kidney transplant recipients as well as in nontransplant patients with chronic kidney disease. It negatively influences the rate of deterioration of graft renal function, graft survival, and more importantly, patient survival. This review analyzes the current knowledge on the management of this crucial aspect in kidney transplantation. The reduction of proteinuria has demonstrated a beneficial effect on kidney function and also on patient survival in nontransplant patients with chronic kidney disease, but unfortunately, to date, it has not been possible to demonstrate the same benefit in the kidney transplant population (although it probably exists). Nevertheless, the appearance of proteinuria in a renal transplant patient must always be followed by an investigation on its etiology, and many times, it should include a graft biopsy to adequately categorize the underlying process responsible for the proteinuria and to establish a correct therapy. Furthermore, in spite of the cause of proteinuria, it should be treated to reduce to normal or near-normal levels with the objective to eliminate or reduce its negative effects on the graft and the cardiovascular system of the patient. The drugs that interfere with the renin-angiotensin-aldosterone system, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, are the cornerstone of the management of this complication, and recently, direct renin inhibitors have added to the armamentarium. Mono-, dual-, and triple-therapy modalities are discussed, as well as other therapies and nonpharmacologic measures.

Bevacizumab (avastin) for corneal neovascularization--corneal light shield soaked application.

PURPOSE: To describe a case where topical bevacizumab (Avastin) was used in an attempt to reduce corneal neovascularization before corneal graft. METHODS: Topical bevacizumab was applied through a corneal light shield for 20 minutes once a week for 11 weeks to the cornea. RESULTS: Corneal vascularization was not reduced. CONCLUSIONS: Topical bevacizumab was not effective in this case at reducing corneal neovascularization.

Endovascular treatment of aneurysmal deterioration in peripheral arterial allografts.

PURPOSE: To report endovascular treatment of 2 patients with aneurysmal deterioration of peripheral arterial allografts. CASE REPORT: Two men (65 and 64 years old) who had undergone an arterial allograft reconstruction for infection of prosthetic infrapopliteal bypass grafts 5 and 7 years ago, respectively, were diagnosed with asymptomatic aneurysmal deterioration of the allografts. Stent-graft repair was successful in both cases, completely excluding the aneurysms. At >or=1 year, continued aneurysm exclusion was confirmed by duplex scan, with no evidence of endoleak, migration, or stenosis. CONCLUSION: Endovascular treatment may be a useful therapeutic option when treating patients with late peripheral allograft deterioration.