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the patient developed nephrotic syndrome by biochemical data and no edema&#46; The renal function remained normal&#46; The oncology service decided to discontinue the drugs temporarily because of the possible causal relationship with the nephrotic syndrome&#46; However&#44; in view of the persistence of proteinuria&#44; it was decided together with the nephrology service&#44; to perform a renal biopsy to establish a histological diagnosis and the possibility of subsequent treatment&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The renal biopsy showed the presence of a renal parenchyma with 8 glomeruli&#44; one of which was sclerotic&#44; with no relevant lesions in the remaining glomeruli&#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The renal interstitium presented moderate fibrosis and areas of tubular atrophy with a discrete nonspecific inflammatory infiltrate&#46; The arteries showed a 25&#37; reduction of their inner diameter due to an atherosclerotic process&#44; together with occasional hyalinosis in arterioles and without damage in the tubular capillaries&#46; The immunohistochemical study did not demonstrate the presence of deposits&#44; but the ultrastructural study &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; identified a 60&#37; fusion of foot processes of the capillary surface with rearrangement of the actin filaments&#46; Combining the clinical and anatomopathological data&#44; it was assumed the diagnosis of a disease due to minimal changes secondary to immunomodulatory treatment&#44; so treatment with prednisone was started at a dose of 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day in a 10-mg regimen every 15 days&#44; reaching a complete remission in the first 4 weeks of treatment&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The drugs inhibiting the &#8220;checkpoint&#8221;&#44; such as nivolumab and ipilimumab&#44; are monoclonal antibodies that act by inhibiting the receptors expressed on the surface of T lymphocytes &#40;CTLA-4 and PD-1&#47;PD-L1&#41;&#44; responsible for inhibiting the stimulation that prevents the attack and the lysis of own cells&#46; Overexpression of these receptors is frequent to evade immune control over tumor proliferation&#46; By blocking these two receptors&#44; there is an increase in the response of the immune system with loss of tolerance to tumor cells with a demonstrated beneficial effect against solid and hematological tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> Previous studies have described the presence of acute renal failure &#40;together with involvement of other organs&#44; mainly glandular in the form of hypophysitis&#44; adrenalitis and sialadenitis&#41; with non-nephrotic proteinuria and predominantly interstitial damage in the renal histological study&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> However&#44; glomerular involvement in this context is scarcely described in the literature&#46; Some cases similar to our patient have been described&#44; highlighting as common elements&#58; the latency time from the beginning of the treatment&#44; the excellent renal response to the administration of steroids and the suspension of the drug&#44; the recurrence of the clinical picture after the reintroduction of the drug&#46; treatment and extensive fusion of foot processes as a histological finding in the ultrastructural study&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">3&#8211;5</span></a> As already described in cases of idiopathic nephrotic syndrome&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> the proposed etiopathogenic mechanism of this entity is a direct damage of podocyte induced by self-reactive T lymphocytes through the expression and function of the podocyte CD80 &#40;B7-1&#41; receptor&#46; The increase in the use of these therapies in oncology&#44; should increase the incidence of cases similar the one presented here&#46; Finally&#44; we believe that it is necessary to monitor renal function and proteinuria in this group of patients in order to make an early diagnosis and establish an effective treatment&#46;</p></span>"
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Letter to the Editor
Immunotherapy in cancer: Great expectations in the world of oncology, but a reason for renal concern
Inmunoterapia en el cáncer: grandes expectativas en el mundo de la oncología, pero un motivo de preocupación renal
Beatriz Redondoa, Candela Moliza, Marina Alonsob, Luis Paz-Aresc, Manuel Pragaa, Enrique Moralesa,
Corresponding author
emoralesr@senefro.org

Corresponding author.
a Servicio de Nefrología, Hospital Universitario 12 de Octubre, Madrid, Spain
b Servicio de Anatomía Patológica, Hospital Universitario 12 de Octubre, Madrid, Spain
c Servicio de Oncología, Hospital Universitario 12 de Octubre, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In recent years&#44; the field of therapy in oncological has expanded significantly with the introduction of new immunomodulatory therapies that have resulted in an important change in patient survival&#59; in addition there is an increase in the spectrum of adverse effects which are the consequence of its own mechanism of action&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 55-year-old woman with a history of active smoking who came to the emergency room for right frontoparietal headache&#44; a non quantified weight loss and progressive focal neurological deterioration in the form of behavioral changes&#44; paraphasia-dysphasias&#44; gait instability and urinary incontinence&#46; A cranial scan was performed&#44; which revealed lesions suggestive of malignancy at the right temporal and left frontal levels with displacement of the midline and subfalcine herniation&#46; 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the patient developed nephrotic syndrome by biochemical data and no edema&#46; The renal function remained normal&#46; The oncology service decided to discontinue the drugs temporarily because of the possible causal relationship with the nephrotic syndrome&#46; However&#44; in view of the persistence of proteinuria&#44; it was decided together with the nephrology service&#44; to perform a renal biopsy to establish a histological diagnosis and the possibility of subsequent treatment&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The renal biopsy showed the presence of a renal parenchyma with 8 glomeruli&#44; one of which was sclerotic&#44; with no relevant lesions in the remaining glomeruli&#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The renal interstitium presented moderate fibrosis and areas of tubular atrophy with a discrete nonspecific inflammatory infiltrate&#46; The arteries showed a 25&#37; reduction of their inner diameter due to an atherosclerotic process&#44; together with occasional hyalinosis in arterioles and without damage in the tubular capillaries&#46; The immunohistochemical study did not demonstrate the presence of deposits&#44; but the ultrastructural study &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; identified a 60&#37; fusion of foot processes of the capillary surface with rearrangement of the actin filaments&#46; Combining the clinical and anatomopathological data&#44; it was assumed the diagnosis of a disease due to minimal changes secondary to immunomodulatory treatment&#44; so treatment with prednisone was started at a dose of 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day in a 10-mg regimen every 15 days&#44; reaching a complete remission in the first 4 weeks of treatment&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The drugs inhibiting the &#8220;checkpoint&#8221;&#44; such as nivolumab and ipilimumab&#44; are monoclonal antibodies that act by inhibiting the receptors expressed on the surface of T lymphocytes &#40;CTLA-4 and PD-1&#47;PD-L1&#41;&#44; responsible for inhibiting the stimulation that prevents the attack and the lysis of own cells&#46; Overexpression of these receptors is frequent to evade immune control over tumor proliferation&#46; By blocking these two receptors&#44; there is an increase in the response of the immune system with loss of tolerance to tumor cells with a demonstrated beneficial effect against solid and hematological tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> Previous studies have described the presence of acute renal failure &#40;together with involvement of other organs&#44; mainly glandular in the form of hypophysitis&#44; adrenalitis and sialadenitis&#41; with non-nephrotic proteinuria and predominantly interstitial damage in the renal histological study&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> However&#44; glomerular involvement in this context is scarcely described in the literature&#46; Some cases similar to our patient have been described&#44; highlighting as common elements&#58; the latency time from the beginning of the treatment&#44; the excellent renal response to the administration of steroids and the suspension of the drug&#44; the recurrence of the clinical picture after the reintroduction of the drug&#46; treatment and extensive fusion of foot processes as a histological finding in the ultrastructural study&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">3&#8211;5</span></a> As already described in cases of idiopathic nephrotic syndrome&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> the proposed etiopathogenic mechanism of this entity is a direct damage of podocyte induced by self-reactive T lymphocytes through the expression and function of the podocyte CD80 &#40;B7-1&#41; receptor&#46; The increase in the use of these therapies in oncology&#44; should increase the incidence of cases similar the one presented here&#46; Finally&#44; we believe that it is necessary to monitor renal function and proteinuria in this group of patients in order to make an early diagnosis and establish an effective treatment&#46;</p></span>"
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Article information
ISSN: 20132514
Original language: English
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