Citations

Introduction and objective: Onconephrology is a new and evolving field that deals with kidney complications in patients with cancer as well as the management of cancer in patients with preexisting kidney disease. With increasing numbers of patients with cancer with kidney-related complications, the field has garnered increased attention. Thus, an annual Greater Toronto Area Onconephrology Interest Group symposium was held in May 2019. The objective of the meeting was to demonstrate the junctures between oncology and nephrology by highlighting recent data regarding (1) kidney impairment in solid organ malignancies, (2) management and treatment of kidney cancer, (3) kidney impairment in hematologic malignancies, (4) malignancy and kidney transplantation, and (5) hyponatremia in patients with cancer. Methods and sources of information: Through a structured presentation, the group explored key topics discussed at a Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on Onconephrology. Expert opinions, clinical trial findings, and publication summaries were used to illustrate patient and treatment-related considerations in onconephrology. Key findings: Kidney complications in patients with cancer are a central theme in onconephrology. An estimated 12% to 25% of patients with solid organ malignancies have chronic kidney disease (CKD), although in certain cancers, the prevalence of CKD is higher. Kidney impairment is also a common complication of some hematologic malignancies. The incidence of renal failure in patients with multiple myeloma is estimated at 18% to 56% and light chain cast nephropathy is seen in approximately 30% of these patients. In addition, there appears to be a bidirectional relationship between kidney cancer and CKD, with some data sets suggesting the risk increases as kidney function declines. Cancer is also of concern in patients with preexisting kidney disease. Kidney transplant recipients have a greater risk of cancer and a higher risk of cancer-related mortality. Kidney complications have also been associated with novel cancer therapies, such as immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy. An estimated 2% to 4% of patients initiating an immune checkpoint inhibitor may develop nephrotoxicity, whereas up to 40% of patients on CAR T-cell therapy experience cytokine release syndrome (CRS). Tumor lysis syndrome and electrolyte abnormalities, such as hyponatremia, have also been reported with CAR T-cell therapy. While the incidence and prevalence of hyponatremia vary depending on the cancer type and serum sodium cutoff point, hyponatremia may be seen in up to 46% of patients hospitalized in cancer centers. Conclusions: Onconephrology is a developing field and the themes arising from this meeting indicate a need for greater collaboration between oncologists and nephrologists. Educational symposia and onconephrology fellowship programs may allow for improved cancer care for patients with kidney disease.

Background. Experience with sequential hematopoietic stem cell transplant (HSCT) and kidney transplant (KT) is limited. Methods. We conducted a retrospective observational study of adult patients who underwent both HSCT and KT at our center, with a median follow-up of 11 y. Results. In our 54 patients cohort (94% autologous HSCT), 36 (67%) patients received HSCT first followed by KT, while 18 (33%) received KT before HSCT. In both groups, AL amyloidosis represented 50% of hematologic diagnosis. Only 4 patients expired due to hematologic disease relapse (2 patients in each group) and only 3 allografts were lost due to hematologic disease recurrence (HSCT first n = 1 and KT first n = 2). Overall 1, 5, and 10 y death-censored graft survival rates were 94%, 94%, and 94%, respectively, for the HSCT first group and 89%, 89%, and 75%, respectively, for the KT first group. Overall 1, 5, and 10 y patients survival rates were 100%, 97% and 90%, respectively, for the HSCT first group and 100%, 76%, and 63%, respectively, for the KT first group. Conclusions. Our study supports safety of sequential KT and HSCT, with improved overall patient survival compared to recipients of HSCT remaining on dialysis and good long-term kidney allograft outcome.

Abstract Gastrointestinal complications of multiple myeloma (MM) treatment are common and include nausea, constipation, and diarrhea. However, acute gastrointestinal events like perforations are rare. We aimed to describe the characteristics and outcomes of patients with MM that had colonic perforations during their treatment. This is a retrospective study that included patients from all three Mayo Clinic sites who had MM and developed a colonic perforation. All patients were diagnosed with colonic perforations based on CT scans and were surgically treated. Patients diagnosed with AL amyloidosis, a perforated colon complicating neutropenic colitis during ASCT and those with perforation due to colonic cancer were excluded. A high dose of dexamethasone was defined as ≥40 mg dexamethasone once a week. Thirty patients met inclusion criteria. All patients received steroids at doses ≥10 mg once weekly prior to the perforation, while four (11%) were on high‐dose dexamethasone without chemotherapy. Fourteen patients were given high doses of dexamethasone. Twenty‐five patients required ostomies with all surviving surgery. Twenty‐four perforations (80%) were associated with diverticulitis. Treatment with steroids was resumed in 23 patients with no further gastrointestinal complications. The median OS was 20 months following perforation (IQR 8–59). Within the same timeframe 5854 patients were treated at Mayo Clinic for MM, making the risk of bowel perforation 0.5%. Intestinal perforations in MM are rare and, in our series, always occurred with dexamethasone ≥10 mg per week. Urgent surgery is lifesaving and resumption of anti‐myeloma treatment appears to be safe.

Abstract Purpose: Rearrangements involving the MYC protooncogene are common in newly diagnosed multiple myeloma, but their prognostic significance is still unclear. The purpose of this study was to assess the impact of MYC rearrangement on clinical characteristics, treatment response, and survival in patients with newly diagnosed multiple myeloma. Experimental Design: This is a retrospective study including 1,342 patients seen in Mayo Clinic in Rochester, MN, from January 2006 to January 2018, who had cytogenetic testing by FISH at diagnosis, including MYC testing using the break apart FISH probe (8q24.1). Results: A rearrangement involving MYC was found in 8% of patients and was associated with elevated β2-microglobulin, ≥50% bone marrow plasma cells, IgA multiple myeloma, and the cooccurrence of trisomies. There were no differences in overall response rates between patients with and without MYC rearrangement when induction chemotherapy was proteasome inhibitor (PI)-based, immunomodulatory drug (IMiD)-based or PI + IMiD-based. Overall survival was shorter in patients with MYC rearrangement compared with patients without MYC rearrangement (5.3 vs. 8.0 years, P < 0.001). MYC rearrangement was associated with increased risk of death on multivariate analysis when high-risk cytogenetic abnormalities, ISS stage III, and ≥70 years of age were included (risk ratio: 1.5; P = 0.007). Conclusions: MYC rearrangement is associated with high disease burden and is an independent adverse prognostic factor in patients with newly diagnosed multiple myeloma.

Abstract Systemic amyloidosis is a rare protein misfolding and deposition disorder leading to progressive organ failure. There are over 15 types of systemic amyloidosis, each caused by a different precursor protein which promotes amyloid formation and tissue deposition. Amyloidosis can be acquired or hereditary and can affect various organs, including the heart, kidneys, liver, nerves, gastrointestinal tract, lungs, muscles, skin and soft tissues. Symptoms are usually insidious and nonspecific resulting in diagnostic delay. The field of amyloidosis has seen significant improvements over the past decade in diagnostic accuracy, prognosis prediction and management. The advent of mass spectrometry‐based shotgun proteomics has revolutionized amyloid typing and has led to the discovery of new amyloid types. Accurate typing of the precursor protein is of paramount importance as the type dictates a specific management approach. In this article, we review each type of systemic amyloidosis to provide the practitioner with practical tools to improve diagnosis and management of these rare disorders.

Background: Clozapine is an atypical antipsychotic with potent alpha-adrenergic blocking properties when administered at high dosages, resulting in vasodilatory shock in overdose settings. Case Summary: A 39-year-old man presented with profound catecholamine- and vasopressin-refractory vasodilatory shock following massive clozapine ingestion. Angiotensin II was initiated when the patient was requiring 2.2 µg/kg/min norepinephrine equivalents of vasopressor support, resulting in a prompt increase in the perfusion pressure. All vasopressors were liberated within 18 hours of angiotensin II initiation, and the patient was discharged with no deficits. Conclusions: Synthetic angiotensin II may represent a therapeutic option for refractory hypotension resulting from high dosages of clozapine or other potent alpha-adrenergic blocking medications.

Performance of endoscopic procedures is associated with a risk of infection from COVID-19. This risk can be reduced by the use of personal protective equipment (PPE). However, shortage of PPE has emerged as an important issue in managing the pandemic in both traditionally high and low-resource areas. A group of clinicians and researchers from thirteen countries representing low, middle, and high-income areas has developed recommendations for optimal utilization of PPE before, during, and after gastrointestinal endoscopy with particular reference to low-resource situations. We determined that there is limited flexibility with regard to the utilization of PPE between ideal and low-resource settings. Some compromises are possible, especially with regard to PPE use, during endoscopic procedures. We have, therefore, also stressed the need to prevent transmission of COVID-19 by measures other than PPE and to conserve PPE by reduction of patient volume, limiting procedures to urgent or emergent, and reducing the number of staff and trainees involved in procedures. This guidance aims to optimize utilization of PPE and protection of health care providers.

Background Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but to the authors' knowledge, limited data exist regarding the safety and efficacy of these agents in transplant recipients. Herein, the authors have reported their experience with 17 patients who were treated with ICIs for metastatic malignancies after undergoing solid organ transplantation. Methods Data were abstracted for solid organ transplant recipients who received ICIs for the treatment of malignancy between January 1, 2016, and September 30, 2019. The authors identified 7 kidney, 8 liver, and 2 heart transplant recipients. Outcomes of interest were adverse drug reactions, cancer progression, and patient survival. Results The most common malignancies treated with ICIs were metastatic squamous cell carcinoma (5 patients; 29%) and hepatocellular carcinoma (5 patients; 29%), which were noted exclusively among liver transplant recipients. The median duration on ICIs was 1.7 months (interquartile range, 0.4‐7.6 months). Five patients (29%) developed adverse reactions, including 4 patients (24%) with immune‐related adverse events(irAEs), 3 patients (18%) with acute allograft rejections, 1 patient (6%) with autoimmune colitis, and 1 patient (6%) with ICI‐induced cardiotoxicity (the patient was a heart transplant recipient). The cumulative incidence of cancer progression was 50% and 69%, respectively, at 6 months and 12 months. Eleven patients (65%) died over the median follow‐up period of 4.6 months (interquartile range, 1.5‐13.2 months) from the time of ICI initiation, with cancer progression being the most common cause of death. Conclusions ICIs can be used as individualized therapy in selected patients who have undergone solid organ transplantation but more studies are needed to determine how best to use these agents to improve outcomes further.