Advances in chronic kidney disease最新文献

Nephrotoxicity associated with immunotherapy is increasingly being encountered in clinical practice. Drugs that augment the immune system to eradicate cancer are revolutionary in the field of oncology. Older generation immunotherapies such as high-dose interleukin and interferon-alpha are now being replaced with more effective immune checkpoint inhibitors and chimeric antigen receptor T-cell therapies, which have shown promising results in numerous clinical trials. Unfortunately, these treatments come with a unique baggage of adverse effects including nephrotoxicity. This onconephrology review summarizes the immunotherapies currently in use and their kidney-related toxicities, pathophysiology, and their management.

Cancer is one of the leading causes of death worldwide. With the introduction of newer chemotherapeutic agents, targeted therapies, and immunotherapy, the prognosis and survival of patients with cancer has remarkably improved. As a result, patients are living longer and experiencing long-term cardiovascular complications. Hypertension is an important risk factor for cardiovascular diseases. Patients with malignancy have multiple etiologies of hypertension development, worsening, or association. This is because of the complex interplay between cancer type, chemotherapeutic agent, patient age, antihypertensive agent, and preexisting comorbidities in the etiology and pathogenesis of hypertension. Management of hypertension in patients with cancer requires accurate blood pressure measurement and considering factors such as adjuvant therapy and cancer-related pain. There are no set guidelines for management of hypertension in this unique cohort, and the therapy should be individualized based on the treatment guidelines for the general population. Onco-hypertension is an emerging subspeciality and entails a multidisciplinary approach between oncology, primary care physicians, nephrology, and cardiology.

The incidence of cancer is higher in patients with end-stage kidney disease (ESKD) than among the general population. Despite this, screening for cancer is generally not cost-effective and may worsen quality of life in these patients. This is due to high mortality rates (patients are not living long enough to reap the benefits of screening), the inaccuracy of cancer screening tests, and the increased risks associated with therapy in patients with ESKD. Specific groups of patients with ESKD who have a longer-than-expected life expectancy or higher-than-expected cancer risk may benefit from screening. These groups include patients on peritoneal dialysis, patients on home hemodialysis, Black and Asian-American patients, transplant-eligible patients, and those at higher risk of cancer including patients with acquired cystic kidney disease, those who have been previously exposed to cytotoxic agents or aristolochic acid, and patients with a genetic predisposition to cancer. In this narrative review, we will examine the prevalence of and risk factors for cancer in patients with ESKD and the effectiveness of cancer screening, and discuss specific situations in which cancer screening may be effective.

Disorders of the divalent ions (magnesium, calcium, and phosphorous) are frequently encountered in patients with cancer. Of these, hypomagnesemia, hypocalcemia, hypercalcemia, and hypophosphatemia are seen most commonly. These electrolyte disturbances may be related to the underlying malignancy or due to side effects of anticancer therapy. When caused by a paraneoplastic process, these abnormalities may portend a poor prognosis. Importantly, the development of severe electrolyte derangements may be associated with symptoms that negatively impact quality of life, preclude the administration of critical chemotherapeutic agents, or lead to life-threatening complications that require hospitalization and emergent treatment. In accordance, prompt recognition and treatment of these disorders is key to improving outcomes in patients living with cancer. This review will discuss selected derangements of the divalent ions seen in this population, with a focus on paraneoplastic and therapy-associated etiologies.

The introduction of novel molecularly targeted therapies in the last 2 decades has significantly improved the patient survival compared to standard conventional chemotherapies. However, this improvement has been accompanied by a whole new spectrum of kidney adverse events. Although known as “targeted,” many of these agents lack specificity and selectivity, and they have a tendency to inhibit multiple targets including those in the kidneys. Early detection and correct management of kidney toxicities is crucial to preserve kidney functions. The knowledge of these toxicities helps guide optimal and continued utilization of these potent therapies. The incidence, severity, and pattern of nephrotoxicity may vary depending on the respective target of the drug. Here, we review the mechanism of action, clinical findings of kidney adverse events, and their proposed management strategies.

As breakthroughs in cancer care are leading to improved long-term outcomes in a subset of advanced cancers, there is a growing population of long-term cancer survivors that are at risk of long-term complications. In this review, we summarize what is known about chronic kidney disease in cancer survivors, focusing on the following high-risk groups: survivors of childhood cancers, stem cell transplant recipients, patients with renal cell carcinoma, patients exposed to cisplatin and other nephrotoxic chemotherapies, and patients receiving immunotherapy for cancer. As new anticancer therapies are developed, more research is needed to understand the long-term risks of kidney function decline and to devise methods to prevent chronic kidney disease.

The association between chronic kidney disease (CKD) and renal cell carcinoma (RCC) is bidirectional and multifactorial. Risk factors such as hypertension, diabetes mellitus, obesity, and smoking increase the risk of both CKD and RCC. CKD can lead to RCC via an underlying cystic disease or oxidative stress. RCC can cause CKD because of the tumor itself, surgical reduction of renal mass (either partial or radical nephrectomy), and perioperative acute kidney injury. Medical therapies such as immune checkpoint inhibitors and vascular endothelial growth factor inhibitors can lead to acute kidney injury and resultant CKD. Clinicians need to be aware of the complex, bidirectional interplay between both diseases.

Childhood cancer therapy carries a high risk of treatment-related toxicities and complications that can impact kidney function. Although many of these adverse effects in the acute setting are well described, less is known about the latent effects of childhood cancer treatments on long-term kidney health. With decades of advancements in treatment protocols for many pediatric malignancies, more children than ever before are surviving into adulthood after being cured of their disease and with lower long-term morbidity. Although there is decreased prevalence of many chronic health conditions in cancer survivors, including gastrointestinal, endocrine, and musculoskeletal disorders, the long-term risk of kidney dysfunction has increased. In this review, we summarize the epidemiology of kidney disease in survivors of childhood cancer and describe the treatment-related risk factors associated with long-term impairment of kidney health. We organize this review by specific kidney disease–related outcomes of interest (chronic electrolyte abnormalities, CKD, proteinuria, and hypertension) to highlight what specific aspects of cancer treatment have been associated with these outcomes. Finally, we conclude by comparing different clinical practice guidelines that exist for long-term kidney function monitoring and include recommendations for when a childhood cancer survivor would benefit from long-term nephrology care.

Conventional chemotherapies remain the mainstay of treatment for many malignancies. Kidney complications of these therapies are not infrequent and may have serious implications for future kidney function, cancer treatment options, eligibility for clinical trials, and overall survival. Kidney adverse effects may include acute kidney injury (via tubular injury, tubulointerstitial nephritis, glomerular disease and thrombotic microangiopathy), long-term kidney function loss and CKD, and electrolyte disturbances. In this review, we summarize the kidney complications of conventional forms of chemotherapy and, where possible, provide estimates of incidence, and identify risk factors and strategies for kidney risk mitigation. In addition, we provide recommendations regarding kidney dose modifications, recognizing that these adjustments may be limited by available supporting pharmacokinetic and clinical outcomes data. We discuss management strategies for kidney adverse effects associated with these therapies with drug-specific recommendations. We focus on frequently used anticancer agents with established kidney complications, including platinum-based chemotherapies (cisplatin, carboplatin, oxaliplatin), cyclophosphamide, gemcitabine, ifosfamide, methotrexate and pemetrexed, among others.