Summary: Objective: The new epilepsy definition adopted by the International League Against Epilepsy (ILAE) includes patients with one unprovoked seizure with a probability of further seizures, similar to the general recurrence risk after two unprovoked seizures, occurring in a 10‐year period. Long‐term follow‐up of patients diagnosed after a single seizure is needed to assess the applicability of the new epilepsy definition in clinical practice.Methods: Patients with newly diagnosed epilepsy were recruited retrospectively with a minimum follow‐up of 10 years. Patients were stratified in two groups depending on the occurrence of one (new definition, ND) or two or more unprovoked seizures (traditional definition, TD) at the time of epilepsy diagnosis and compared for disease characteristics and factors predicting seizure recurrence. The primary outcome was the occurrence of a new unprovoked seizure during follow‐up in the ND group. The secondary outcome was the achievement of an early remission in both groups.Results: Among 1,006 patients with newly diagnosed epilepsy, 152 (15.1%) were diagnosed after a single seizure. Compared to patients diagnosed using the TD, patients diagnosed according to the ND showed a higher proportion of subjects with an abnormal neurologic examination (19.9% vs. 13.7%, p = 0.0504) and with focal seizures (69.3% vs. 60.4%, p = 0.0021). The two samples differed in the presence of at least one of the factors predicting seizure recurrence (focal seizures or abnormal findings in at least one among the following: neurologic examination, electroencephalography [EEG], and neuroimaging) (94.6% vs. 89.1%, p = 0.0376). Long‐term recurrence in patients diagnosed with the new definition was 83.6% at 10 years and 89.1% at 15 years. The probability of early remission did not differ between the two groups.Significance: Our results support the applicability of the new epilepsy definition in clinical practice. Individual patient characteristics and a personalized diagnostic approach can justify treatment after a single unprovoked seizure.

Molecular targeted therapy has revolutionized cancer treatment by significantly improving patient survival compared with standard conventional chemotherapies. The use of these drugs targets specific molecules or targets, which block growth and spread of cancer cells. Many of these therapies have been approved for use with remarkable success in breast, blood, colorectal, lung, and ovarian cancers. The advantage over conventional chemotherapy is its ability to deliver drugs effectively with high specificity while being less toxic. Although known as “targeted,” many of these agents lack specificity and selectivity, and they tend to inhibit multiple targets, including those in the kidneys. The side effects usually arise because of dysregulation of targets of the inhibited molecule in normal tissue. The off-target effects are caused by drug binding to unintended targets. The on-target effects are associated with inhibition toward the pathway reflecting inappropriate inhibition or activation of the intended drug target. 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. This review summarizes the different types of molecular targeted therapies used in the treatment of cancer and the incidence, severity, and pattern of nephrotoxicity caused by them, with their plausible mechanism and proposed treatment recommendations.

The incidence of tumors increases significantly in individuals with chronic kidney disease (CKD), particularly among those undergoing dialysis. This dialysis-associated condition not only impacts therapy but also influences the prognosis of oncological patients, contributing to heightened mortality rates related to both cancer and non-cancer causes. Importantly, it stands as a primary factor leading to suboptimal utilization of therapies. Dosage adjustment for many types of chemotherapy is a necessity in patients with kidney impairment. However, due to a lack of comprehensive knowledge about the pharmacokinetic and pharmacodynamic properties of these drugs in dialysis, adjustments are often made empirically, and in many cases, chemotherapy is avoided altogether. In this review, we highlight the current challenges and gaps in knowledge, and emphasize the imperative need for dedicated research to establish evidence-based guidelines for chemotherapy management in this vulnerable patient population. Graphical

Renal Cell Carcinoma (RCC) is the most frequent malignancy encountered in general nephrology practice; when kidney disease develops in the setting of RCC, it may limit long-term outcomes, patients often dying of a non-cancer-related complication of kidney disease. There is a reciprocal relationship between renal cancer and kidney; chronic kidney disease can increase the risk of developing kidney cancer, and patients with RCC often experience renal impairment owing to pre-existing chronic kidney disease (CKD), hypertension (HTN), diabetes mellitus (DM), and/or other medically challenging comorbidities, or risk factors for CKD. Nephrologists should be involved in all aspects of RCC patients’ care, from pre-nephrectomy evaluation, to management of post-nephrectomy CKD, through the recognition and management of anticancer drugs-related kidney toxicity. This collaborative approach to RCC care will further improve the clinical outcomes of kidney cancer patients.

Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) effective in non- small cell lung cancer (NSCLC) with EGFR mutations. Since the drug is primally eliminated by the fecal route no dose adjustment is needed in patient with chronic-kidney disease (CKD); despite this there is limited data about its safety in cancer patients with end-stage renal disease (ESRD). Herein, we reported a case report of a 77-year-old woman, diagnosed in 2018 with lung adenocarcinoma EGFR mutated with lymph nodal and cerebral metastasis, who started Osimertinib 80 mg/day. She under- went 41 cycles of therapy with no Osimertinib interruptions, no severe toxicities and obtaining complete radiological response. We conclude that Osimertinib has an acceptable safety profile also in cancer patients with ESRD not undergoing hemodialysis (HD).