1.
Renal Toxicity of Systemic Therapy for Renal Cell Carcinoma.
Jaimes, EA
Seminars in nephrology. 2020;(1):49-58
Abstract
The incidence of kidney cancer has been increasing steadily and, until recently, there was a substantial lack of effective therapies for a cancer that is now among the 10 most common cancers in men and women. During the past 10 years, novel therapies have been developed including antiangiogenic drugs targeting vascular endothelial growth factor and its receptors, immune checkpoint inhibitors, and mammalian target of rapamycin inhibitors that have resulted in a significant improvement in clinical outcomes in a traditionally difficult-to-treat cancer. These new drugs, however, also have important side effects and toxicities that often have an impact on the treatment of these patients. The use of anti-angiogenic drugs often results in the development of hypertension and, less frequently, varying degrees of proteinuria including nephrotic range proteinuria. A variety of agents are used for the treatment of hypertension and proteinuria including blockers of the renin angiotensin system and calcium channel blockers, but there are no randomized clinical trials comparing different therapeutic agents in these patients. Immune checkpoint inhibitors have become one of the cornerstones of therapy in kidney cancer, but their use is linked to a variety of side effects that affect almost every organ and resemble autoimmune diseases. In the kidney, these drugs can induce acute interstitial nephritis in close to 5% of patients with varying degrees of severity that in some cases require discontinuation of treatment and systemic treatment with corticosteroids. Although mammalian target of rapamycin inhibitors now also are part of the therapeutic armamentarium available for these patients, all clinical trials have been performed in patients with normal renal function and therefore their effects in patients with abnormal renal function are not known.
2.
Primary hypothyroidism and isolated ACTH deficiency induced by nivolumab therapy: Case report and review.
Zeng, MF, Chen, LL, Ye, HY, Gong, W, Zhou, LN, Li, YM, Zhao, XL
Medicine. 2017;(44):e8426
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Abstract
RATIONALE Nivolumab is a monoclonal IgG antibody blocking programmed death receptor-1 (PD1), leading to restoration of the natural T-cell-mediated immune response against the cancer cells. However, it also causes plenty of autoimmune-related adverse events, which often involves endocrine system. PATIENT CONCERNS A 54-year-old male with renal clear cell carcinoma was treated with nivolumab intravenously. Routine monitoring showed elevated thyroid-stimulating hormone and low free thyroxine after the 6th administration of nivolumab. After the 12th administration, he developed general fatigue, recurrent hypoglycemia, and relative hypotension. Laboratory tests showed low sodium, low morning cortisol without correspondence increase of corticotrophin (ACTH). Other pituitary hormones were normal. MRI showed no space-occupying lesions, but heterogeneous enhancement of the pituitary gland. DIAGNOSES Primary hypothyroidism and isolated ACTH deficiency. The etiologies were assumed to be nivolumab induced autoimmune lymphocytic thyroiditis and hypophysitis, respectively. INTERVENTIONS Hormone replacements with levothyroxine and acetate cortisone were given orally. Nivolumab was adjusted to lower dose and longer interval. OUTCOMES The patient felt good after adequate replacement. Nivolumab was returned to routine dose and interval six months later. And the metastasis was not obviously progressed during this time. LESSONS The present report provides the first detailed presentation of combined hypothyroidism and isolated ACTH deficiency induced by nivolumab. Adrenal deficiency often develops insidiously. We suggest routine monitoring of fasting blood-glucose, blood pressure and serum sodium as well as thyroid function during nivolumab and other cancer immunotherapies. When unexpected fatigue, hypoglycemia, hypotension or hyponatremia appeared, adrenal deficiency should be taken into consideration.
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The Therapeutic Aspects of the Endocannabinoid System (ECS) for Cancer and their Development: From Nature to Laboratory.
Khan, MI, Sobocińska, AA, Czarnecka, AM, Król, M, Botta, B, Szczylik, C
Current pharmaceutical design. 2016;(12):1756-66
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Abstract
The endocannabinoid system (ECS) is a group of neuromodulatory lipids and their receptors, which are widely distributed in mammalian tissues. ECS regulates various cardiovascular, nervous, and immune system functions inside cells. In recent years, there has been a growing body of evidence for the use of synthetic and natural cannabinoids as potential anticancer agents. For instance, the CB1 and CB2 receptors are assumed to play an important role inside the endocannabinoid system. These receptors are abundantly expressed in the brain and fatty tissue of the human body. Despite recent developments in molecular biology, there is still a lack of knowledge about the distribution of CB1 and CB2 receptors in the human kidney and their role in kidney cancer. To address this gap, we explore and demonstrate the role of the endocannabinoid system in renal cell carcinoma (RCC). In this brief overview, we elucidate the therapeutic aspects of the endocannabinoid system for various cancers and explain how this system can be used for treating kidney cancer. Overall, this review provides new insights into cannabinoids' mechanisms of action in both in vivo and in vitro models, and focuses on recent discoveries in the field.
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Obesity, interrelated mechanisms, and exposures and kidney cancer.
Moyad, MA
Seminars in urologic oncology. 2001;(4):270-9
Abstract
Obesity has been shown to increase the risk or be associated with numerous conditions from cardiovascular disease and type II diabetes to erectile dysfunction and osteoarthritis. Obesity may also be associated with numerous cancers, and kidney cancer or renal-cell cancer (RCC) may have one of the strongest correlations to obesity compared with cancer at any other site. Almost every epidemiologic investigation has demonstrated an association that tends to affect women more than men, but both genders are impacted. In general, past studies suggest that with increasing weight, a threshold point exists whereby a certain range of body mass index dramatically changes risk. Men and women at the most extreme ends of obesity tend to have the highest risk or only risk in past studies. Individuals at the more extreme ends of obesity may be affected by an almost indefinite number of mechanisms and exposures that could determine incidence and possibly prognosis. For example, higher estrogen levels, elevated insulin levels, a greater concentration of growth factors in adipose tissue, hypertension, cholesterol metabolism abnormalities, and immune malfunction are just some of the potential mechanisms that may increase kidney cancer risk. Obese individuals may also have lower serum levels of vitamin D and engage in less physical activity. Smoking or genetic predisposition to RCC may synergistically contribute to the effect of obesity on risk. The potential mechanisms and associations are numerous and complex. Regardless of the actual cancer risk now and in the future, the overall effect of obesity on general health is clear, and this should be kept in mind in the discussion between health professional and patient.