Letter to the Editor
The need for renal biopsy in oncology patients on check-point inhibitors check-point inhibitors: New triggers for extracapillary glomerulonephritis extracapillary glomerulonephritis
La necesidad de la biopsia renal en paciente oncológico con inhibidores de check-point: nuevos trigger para glomerulonefritis extracapilar
M. Dolores Sanchez de la Nieta Garcia
, Almudena Juez del Pozo, José Antonio Cortés Toro, Antolina Rodríguez Moreno, Clara García Carro, Elena Ruiz Ferreras, Ana Isabel Sánchez Fructuoso
Corresponding author
Hospital Clínico San Carlos, Ciudad Real, Spain
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Dolores Sanchez de la Nieta Garcia, Almudena Juez del Pozo, José Antonio Cortés Toro, Antolina Rodríguez Moreno, Clara García Carro, Elena Ruiz Ferreras, Ana Isabel Sánchez Fructuoso" "autores" => array:7 [ 0 => array:4 [ "nombre" => "M. Dolores" "apellidos" => "Sanchez de la Nieta Garcia" "email" => array:1 [ 0 => "sanchezdelanieta@senefro.org" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Almudena" "apellidos" => "Juez del Pozo" ] 2 => array:2 [ "nombre" => "José Antonio" "apellidos" => "Cortés Toro" ] 3 => array:2 [ "nombre" => "Antolina" "apellidos" => "Rodríguez Moreno" ] 4 => array:2 [ "nombre" => "Clara" "apellidos" => "García Carro" ] 5 => array:2 [ "nombre" => "Elena" "apellidos" => "Ruiz Ferreras" ] 6 => array:2 [ "nombre" => "Ana Isabel" "apellidos" => "Sánchez Fructuoso" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Hospital Clínico San Carlos, Ciudad Real, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La necesidad de la biopsia renal en paciente oncológico con inhibidores de check-point: nuevos trigger para glomerulonefritis extracapilar" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 682 "Ancho" => 905 "Tamanyo" => 254626 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0315" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Masson's trichrome. Glomerulus with epithelial crescent.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Checkpoint inhibitors (CPI) have revolutionised cancer treatment. They act by inhibiting T-lymphocyte (TL) receptors, cytotoxic T-lymphocyte antigen 4 (CTLA4) or programmed cell death 1 (PD1) receptors or their ligands, triggering TL dysregulation and hyperactivation, which causes immune-related adverse events (irAE). In the kidneys, the most common is immune-mediated interstitial nephritis, but there is also pauci-immune glomerulonephritis, podocytopathies and C3 glomerulopathy, which worsen the prognosis.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–6</span></a> We present a case of pauci-immune glomerulonephritis (PIGN) during treatment with durvalumab, antiPD-L1, in a patient with squamous cell carcinoma of the lung.</p><p id="par0010" class="elsevierStylePara elsevierViewall">This was a 71-year-old male with a history of hypertension, type 2 diabetes, dyslipidaemia and squamous cell carcinoma of the lung (G2 pT3 pN1, PD-L1<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>1%) diagnosed in 2018; surgical treatment and chemotherapy with four cycles of cisplatin and vinorelbine. Maintenance treatment with durvalumab, 12 cycles, until 14/11/2019, remaining disease free (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">On 17/11/2019 he was admitted for acute renal failure; creatinine 4.5<span class="elsevierStyleHsp" style=""></span>mg/dl, microhaematuria (300 red blood cells/μl), clinical and analytical nephrotic syndrome (proteinuria 6<span class="elsevierStyleHsp" style=""></span>g/day, albumin 2.2<span class="elsevierStyleHsp" style=""></span>mg/dl). Immunological study normal/negative; renal biopsy: 21 glomeruli, 6<span class="elsevierStyleHsp" style=""></span>globally sclerotic. Inflammatory hypercellularity in capillary lumens, mononucleated, focally neutrophils, fragmented red blood cells and leucocytoclastic phenomenon. Four glomeruli with epithelial crescents. Interstitial fibrosis, tubular atrophy and mild chronic inflammation. The arteries and arterioles appeared normal. Direct immunofluorescence no IgA, IgG, IgM, C3, C1q, kappa, lambda deposits. Diagnosis: pauci-immune glomerulonephritis with extracapillary proliferation in 27% of glomeruli. He was started on intravenous steroids (500<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>3 days) orally at a dose of 1<span class="elsevierStyleHsp" style=""></span>mg/kg/day and adjusted intravenous cyclophosphamide (500<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>).</p><p id="par0020" class="elsevierStylePara elsevierViewall">After one month, outpatient follow-up with oral steroids and cyclophosphamide; creatinine 3–3.5<span class="elsevierStyleHsp" style=""></span>mg/dl, CKD-EPI 16.5–18<span class="elsevierStyleHsp" style=""></span>ml/min, nephrotic proteinuria and microhaematuria.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Readmission after second bolus of cyclophosphamide; creatinine 7.14<span class="elsevierStyleHsp" style=""></span>mg/dl, urea 319<span class="elsevierStyleHsp" style=""></span>mg/dl and proteinuria 4.18<span class="elsevierStyleHsp" style=""></span>g/24<span class="elsevierStyleHsp" style=""></span>h without nephrotic syndrome, severe haematuria. Renal replacement therapy (RRT) was started; intermittent haemodialysis, maintaining a diuresis of 1500–2000<span class="elsevierStyleHsp" style=""></span>cc/day. Subsequently, he continued intravenous cyclophosphamide and a regular haemodialysis programme, with close follow-up. We have noted a decrease in proteinuria to <1.5<span class="elsevierStyleHsp" style=""></span>g/day, diuresis 2<span class="elsevierStyleHsp" style=""></span>l and a CrCl 12–18<span class="elsevierStyleHsp" style=""></span>ml/min with no need for RRT until now and oncological disease in complete remission.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Checkpoints are regulators of the TL immune response. Their blockade with immunotherapy promotes a state of lymphocyte dysregulation, leading to hyperstimulation of TL and better control over tumour cells. However, their main drawback is irAE, exacerbating autoimmune diseases such as PIGN. PIGN is characterised by positive serum antineutrophil cytoplasmic antibodies (ANCA), sometimes, as in our patient, they are negative, speculating that they are ANCA against another epitope or other undetected autoantibodies.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">PIGN has been associated with aberrant PD1 expression in some subjects and increased TL hyperactivity, with the risk of developing PIGN increased by immunotherapy treatment. In our case we could postulate that there was this aberrant expression which triggered PIGN,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and stopping the immunotherapy combined with immunosuppressive treatment was able to control the TL hyperactivity, which then led to remission of the PIGN.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Polymorphisms in PDCD1 (the gene that encodes PD1) have also been described, which increase susceptibility for developing PIGN; therefore, a genetic analysis could be useful to prevent the development of PIGN in patients requiring treatment with CPI and to consider other treatments.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The close relationship between oncology and nephrology leads to early renal biopsy and assessment by nephrology, with early diagnosis increasing renal and overall survival.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 682 "Ancho" => 905 "Tamanyo" => 262199 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0310" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Masson's trichrome. Glomerulus with global endocapillary hypercellularity, leucocytoclasia and red cell fragmentation in the capillary tuft close to the vascular pole.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 682 "Ancho" => 905 "Tamanyo" => 254626 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0315" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Masson's trichrome. Glomerulus with epithelial crescent.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: review of the literature and personalized risk-based prevention strategy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Haanen" 1 => "M.S. Ernstoff" 2 => "Y. Wang" 3 => "A.M. Menzies" 4 => "I. Puzanov" 5 => "P. Grivas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.annonc.2020.03.285" "Revista" => array:6 [ "tituloSerie" => "Ann Oncol." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 6 | 13 |
| 2024 October | 57 | 31 | 88 |
| 2024 September | 51 | 36 | 87 |
| 2024 August | 76 | 63 | 139 |
| 2024 July | 52 | 21 | 73 |
| 2024 June | 46 | 39 | 85 |
| 2024 May | 63 | 53 | 116 |
| 2024 April | 67 | 31 | 98 |
| 2024 March | 81 | 31 | 112 |
| 2024 February | 191 | 85 | 276 |
| 2024 January | 13 | 21 | 34 |
