Since angiogenesis plays a key role in tumor growth, progression and metastasization, anti-vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) agents have been developed over the years as anticancer agents, and have changed, for the better, the natural history of a number of cancer types. In the present review, the renal safety profile of presently available agents targeting either VEGF or VEGFRs will be discussed, together with the peculiarities related to their clinical use in patients with impaired renal function, or even in dialysis. Indeed, renal toxicity (especially, but not exclusively, hypertension and proteinuria) are quite commonly observed with these agents, and may be increased by the concomitant use of cytoxic chemotherapeutics. Despite all the above, kidney impairment or dialysis must not be regarded di per se as reasons not to administer or to stop an active anticancer treatment, especially considering the possibility of a significant survival improvement in many cancer patients treated with these agents.
Acute kidney injury (AKI) is a common complication of cancer that occurs in up to 50% of neoplastic patients during the natural history of their disease; furthermore, it has a huge impact on key outcomes such as overall prognosis, length of hospitalization and costs. AKI in cancer patients has different causes, either patient-, tumour- or treatment-related. Patient-related risk factors for AKI are the same as in the general population, whereas tumour-related risk factors are represented by compression, obstruction, direct kidney infiltration from the tumour as well by precipitation, aggregation, crystallization or misfolding of paraprotein (as in the case of multiple myeloma). Finally, treatment-related risk factors are the most common observed in clinical practice and may present also with the feature of tumour lysis syndrome or thrombotic microangiopathies. In the absence of validated biomarkers, a multidisciplinary clinical approach that incorporates adequate assessment, use of appropriate preventive measures and early intervention is essential to reduce the incidence of this life-threatening condition in cancer patients.
EGFR and HER2 are found overexpressed and/or activated in many different human malignancies (e.g. breast and colon cancer), and a number of drugs specifically targeting these two tyrosine kinases have been developed over the years as anticancer agents. In the present review, the renal safety profile of presently available agents targeting either HER2 or EGFR will be discussed, together with the peculiarities related to their clinical use in patients with impaired renal function, or even in dialysis. Indeed, even though renal toxicity is not so common with these agents, it may nevertheless happen, especially when these agents are combined with traditional chemotherapeutic agents. As a whole, kidney impairment or dialysis should not be regarded per se as reasons not to administer or to stop an active anti-HER or anti-EGFR anticancer treatment, especially given the possibility of significantly improving the life expectancy of many cancer patients with the use of these agents.
Acute kidney injury (AKI), either of pre-renal, renal or post-renal origin, is an important complication in cancer patients, resulting in worse prognosis, withdrawal from effective oncological treatments, longer hospitalizations and increased costs. The aim of this article is to provide a literature review of general and cause-specific treatment strategies for AKI, providing a helpful guide for clinical practice. We propose to classify AKI as patient-related, cancer-related and treatment-related in order to optimize therapeutic interventions. In the setting of patient-related causes, proper assessment of hydration status and avoidance of concomitant nephrotoxic medications is key. Cancer-related causes mainly encompass urinary compression/obstruction, direct tumoural kidney involvement and cancer-induced hypercalcaemia. Rapid recognition and specific treatment can potentially restore renal function. Finally, a pre-treatment comprehensive evaluation of risks and benefits of each treatment should always be performed to identify patients at high risk of treatment-related renal damage and allow the implementation of preventive measures without losing the potentialities of the oncological treatment. Considering the complexity of this field, a multidisciplinary approach is necessary with the goal of reducing the incidence of AKI in cancer patients and improving patient outcomes. The overriding research goal in this area is to gather higher quality data from international collaborative studies.
Chronic kidney disease mineral bone disorder (CKD-MBD) is a condition characterized by alterations of calcium, phosphate, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) metabolism that in turn promote bone disorders, vascular calcifications and increase cardiovascular (CV) risk. Nephrologists' awareness of diagnostic, prognostic, and therapeutic tools to manage CKD-MBD plays a primary role in adequately preventing and managing this condition in clinical practice. a national survey (composed of 15 closed questions) was launched to inquire about the use of bone biomarkers in the management of CKD-MBD patients by Nephrologists and to gain knowledge about the implementation of guideline recommendations in clinical practice. one hundred and six Italian nephrologists participated in the survey for an overall response rate of about 10%. Nephrologists indicated that the laboratories of their hospitals were able to satisfy request of ionized calcium levels, 105 (99.1%) of both PTH and ALP, 100 (94.3%) of 25(OH)D, and 61 (57.5%) of 1,25(OH)2D; while, most laboratories did not support the requests of biomarkers such as FGF-23 (intact: 88.7% and c-terminal: 93.4%), Klotho (95.3%; soluble form: 97.2%), TRAP-5b (92.5%), CTX (71.7%) and P1NP (88.7%). An interesting data regarding Italian nephrologist's behavior to start treatment of sHPT, the majority of clinicians used KDOQI guidelines (n = 55, 51.9%). In contrast, only 40 nephrologists (37.7%) relied on KDIGO guidelines which recommended referring to values of PTH between 2 and 9 times the upper limit of the normal range. Results point out a marked heterogeneity in the management of CKD-MBD by clinicians as well as a suboptimal implementation of guidelines in Italian clinical practice.
OGon behalf of the SIN-SIOMMMS Bone Biopsy Promoting Group
on behalf of the SIN-SIOMMMS Bone Biopsy Promoting Group
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Bone Biopsy (BB) with histomorphometric analysis still represents the gold standard for the diagnosis and classification of different forms of renal osteodystrophy. Bone biopsy is the only technique able to provide comprehensive information on all bone parameters, measuring static and dynamic parameters of turnover, cortical and trabecular microarchitecture, and mineralization defects. In nephrological practice, bone biopsy yields relevant indications to support therapeutic choices in CKD, heavily impacting the management and prognosis of uremic patients. Unfortunately, the use of bone biopsy has decreased; a lack of expertise in performing and interpreting, perceived procedure invasiveness and pain, and reimbursement issues have all contributed to this decline. Nevertheless, both bone biomarkers and instrumental images cannot be considered reliable surrogates for histological findings, being insufficiently accurate to properly evaluate underlying mineral and bone disorders. This is a multidisciplinary position paper from the Nephrology and Osteoporosis Italian Scientific Societies with the purpose of restating the role of bone biopsy in CKD patient management and of providing strong solutions to allow diffusion of this technique in Italy, but potentially also in other countries. The Italian approach through the optimization and standardization of bone biopsy procedure, the construction of the Italian Hub and Spoke network, and a request for adjustment and national homogenization of reimbursement to the Italian Health Ministry has led the way to implement bone biopsy and to improve CKD patient management and prognosis.