Letter to the Editor
Pulmonary-renal syndrome as a clinical expression of multiple myeloma
Síndrome pulmón-riñón como una expresión clínica de mieloma múltiple
Joana Gameiro
, Sofia Jorge, José António Lopes, António Gomes da Costa
Corresponding author
Service of Nephrology and Renal Transplantation, Department of Medicine Centro Hospitalar Lisboa Norte, EPE Av. Prof. Egas Moniz, 1649-035 Lisboa, Portugal
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Prof. Egas Moniz, 1649-035 Lisboa, Portugal" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome pulmón-riñón como una expresión clínica de mieloma múltiple" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 721 "Ancho" => 960 "Tamanyo" => 155067 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Immunofluorescence for κ-light chain – diffuse linear staining of the tubular basement membranes.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Pulmonary-renal syndrome (PRS) is defined as pulmonary and renal failure, and is caused by immunological and non-immunological diseases. Although the most frequent immunological causes for PRS are small vessel vasculitis and lupus,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> other causes have to be considered.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Here, we present the case of a 35-year-old, black, previously healthy woman referred from Cape Verde to our Department to investigate renal failure (creatinemia 2.5<span class="elsevierStyleHsp" style=""></span>mg/dL), hypertension, lower limbs edema, foamy urine, anemia (Hb 11.5<span class="elsevierStyleHsp" style=""></span>mg/dL), and bilateral arthralgias developing within the last 6 months. She had no family history of renal disease neither respiratory, neurologic or gastrointestinal symptoms nor alopecia, rash, oral ulcers, photosensitivity, hematuria or recent drug use. At admission, she was polypneic, hypertensive, aeodematous, oligoanuric, presented bilateral fine pulmonary crackles, and bilateral erythematous lesions in thighs. Laboratory revealed anemia (Hb 7.1<span class="elsevierStyleHsp" style=""></span>g/dL), leukocytosis with neutrophilia (16.670/mm3; 91.9%), elevated C-reactive protein (12.2<span class="elsevierStyleHsp" style=""></span>mg/dL), elevated erythrocyte sedimentation rate (70<span class="elsevierStyleHsp" style=""></span>mm 1st h), renal insufficiency (uremia 247<span class="elsevierStyleHsp" style=""></span>mg/dL, creatininemia 7.5<span class="elsevierStyleHsp" style=""></span>mg/dL), and of NT pro-BNP (>105<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>pg/mL). Blood gas test showed severe hypoxemia. Urinalysis showed haematuria (200/mm3) and proteinuria 300<span class="elsevierStyleHsp" style=""></span>mg/dL, without casts. Chest X-ray revealed bilateral diffuse opacities (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), and chest CT suggested pulmonary hemorrhage. Ultrasonogram showed normal sized kidneys with increased echogenicity. She required mechanical ventilation and hemodialysis. Bronchofibroscopy revealed alveolar hemorrhage, and plasmapheresis was initiated.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Complementary investigation showed nephrotic range proteinuria (4.7<span class="elsevierStyleHsp" style=""></span>g/24<span class="elsevierStyleHsp" style=""></span>h). Serum protein electrophoresis showed an alpha2 spike and hypogamaglobulinemia. Serum complement was normal and serology for lupus, vasculitis and cryoglobulinemia, as well as for human immunodeficiency virus, hepatitis B and C infections were negative. Echocardiogram revealed a type II diastolic dysfunction. A renal biopsy was performed and revealed nodular glomerulosclerosis. Immunofluorescence revealed linear staining for kappa light chains along the tubular basement membrane and also in the glomerulus, allowing the diagnosis of light chain deposits disease (LCDD) (<a class="elsevierStyleCrossRefs" href="#fig0010">Figs. 2 and 3</a>). Serum immunofixation revealed a kappa light chain band, and urine immunofixation revealed Bence-Jones kappa. Bone marrow biopsy and aspirate showed normocellular marrow with 10% monoclonal plasmocytosis. Therefore, multiple myeloma was diagnosed. She received chemotherapy and an autologous hematopoietic cell transplant, achieving maintained complete hematological response. At one-year of follow-up, she remains dialysis-dependent.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The initial presentation led us to consider an immunological cause for the pulmonary renal syndrome, despite the negative immunological results, which might occur in 10–20% of the PRS of immunological origin. The unexpected nodular glomerulosclerosis on the kidney biopsy led us to further investigate an hematological disease, because together with diabetes mellitus and smoking, light or heavy chain deposits disease is one of the main causes of nodular glomerulosclerosis. The investigation of the hematological disease was consistent with a diagnosis of multiple myeloma, according to the International Myeloma Working Group criteria.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">LCDD is a rare renal manifestation of plasma cell disorders.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a> LCDD is a systemic disease with renal, cardiac, pulmonary, hepatic and gastrointestinal involvement.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">3–5</span></a> Renal involvement is the most frequent and manifests as nephrotic syndrome and renal insufficiency, typically rapidly progressive. Renal biopsy typically reveals nodular glomerulosclerosis and thickening of the tubular basement membrane. In 80% of the cases it is characterized by the deposition of kappa light chains along the glomerular capillaries, nodules and the tubular basement membrane. Electron microscopy reveals granular deposits.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">4,6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Although we cannot conclude on the cause of the pulmonary hemorrhage, because of the lack of pulmonary biopsy, we speculate on pulmonary tissue LC deposition, as this seems to be a case of systemic LC deposition: kidney, lung, heart, skin and articulations. This case highlights that LCDD should be kept in mind in the differential diagnosis of PRS.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 697 "Ancho" => 960 "Tamanyo" => 57298 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Chest X-ray revealing bilateral diffuse opacity, predominantly in the right hemithorax.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 721 "Ancho" => 960 "Tamanyo" => 155067 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Immunofluorescence for κ-light chain – diffuse linear staining of the tubular basement membranes.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 675 "Ancho" => 900 "Tamanyo" => 149286 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Immunofluorescence for κ-light chain reveals diffuse linear staining of the glomerular basement membranes.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0035" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pulmonary-renal syndromes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G.G. 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Appel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2001" "volumen" => "12" "paginaInicial" => "1482" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11423577" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0055" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Light chain deposit disease: a frequent cause of diagnostic difficulty" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Hall" 1 => "D. 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Milleron" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.00134406" "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "2007" "volumen" => "29" "paginaInicial" => "1057" "paginaFinal" => "1060" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17470625" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack297278" "titulo" => "Acknowledgements" "texto" => "<p id="par0035" class="elsevierStylePara elsevierViewall">The authors would like to acknowledge Helena Viana, MD and Fernanda Carvalho, MD, who were responsible for the kidney biopsy results and supplied the images.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000003700000004/v1_201708310023/S2013251417300482/v1_201708310023/en/main.assets" "Apartado" => array:4 [ "identificador" => "35436" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000003700000004/v1_201708310023/S2013251417300482/v1_201708310023/en/main.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251417300482?idApp=UINPBA000064" ]
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| 2019 June | 40 | 26 | 66 |
| 2019 May | 53 | 26 | 79 |
| 2019 April | 92 | 22 | 114 |
| 2019 March | 47 | 24 | 71 |
| 2019 February | 44 | 27 | 71 |
| 2019 January | 46 | 21 | 67 |
| 2018 December | 131 | 41 | 172 |
| 2018 November | 247 | 18 | 265 |
| 2018 October | 236 | 18 | 254 |
| 2018 September | 98 | 18 | 116 |
| 2018 August | 62 | 13 | 75 |
| 2018 July | 83 | 15 | 98 |
| 2018 June | 78 | 10 | 88 |
| 2018 May | 78 | 21 | 99 |
| 2018 April | 165 | 14 | 179 |
| 2018 March | 162 | 10 | 172 |
| 2018 February | 114 | 11 | 125 |
| 2018 January | 118 | 7 | 125 |
| 2017 December | 75 | 6 | 81 |
| 2017 November | 61 | 9 | 70 |
| 2017 October | 27 | 4 | 31 |
| 2017 September | 56 | 16 | 72 |
| 2017 August | 2 | 1 | 3 |
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