Clinicopathological characteristics of renal light chain deposition disease coexisted with cast nephropathy / 中华肾脏病杂志

Objective To investigate the clinicopathological characteristics of renal light chain deposition disease coexisted with cast nephropathy (LCDD&LCN).Methods Patients with LCDD&LCN (n=10),isolated LCDD (I-LCDD,n=21) and isolated LCN(I-LCN,n=17) diagnosed byrenal biopsy in Peking University First Hospital from January 1,2000 to March 31,2018 were enrolled,and all cases were examined by light microscopy,immunofluorescence (IF) (including light chain) and electron microscopy (EM).The semi-quantitative evaluation of the main features of renal pathology was performed.The clinical manifestations and pathological features were reviewed and compared.Results LCDD&LCN was more prevalent in middle-aged males.Nine patients showed acute renal insufficiency with small molecular proteinuria (97.1％) and microscopic hematuria.The hematologic diseases included 9 patients of multiple myeloma.The type of monoclonal light chain in serum and urine by immunofixation electrophoresis showed λ dominant (5/8).By light microscopy,glomerular lesions presented with mild mesangial proliferation in most patients,and only one of them displayed mesangial nodular sclerosis.At the same time,acute tubular injury with light chain casts was the prominent feature,and the clinical manifestations and histological features of LCDD&LCN were similar to that of I-LCN.IF revealed linear staining of monoclonal light chain along the glomerular basement membrane (GBM),tubular basement membrane (TBM) and Bowman's capsule,and also positive in tubular casts.By electron microscopy,diffuse powder-like or granular electron-dense deposits located in the inner side of the GBM,the outer layer of the TBM,renal interstitium and arteriolar walls were observed.Conclusions Patients with LCDD&LCN manifest as acute renal insufficiency,and the majority have multiple myeloma.The pathology of LCDD&LCN possesses the features of both I-LCDD and I-LCN.The IF stain of light chains(κ,λ) and ultrastructural examination by electron microscopy are the inevitable methods for the diagnosis of LCDD&LCN.

Enfermedad renal por depósito idiopático de cadenas livianas. Caso clínico / Kidney involvement in idiopathic light chain disease. Report of one case

El Mieloma Múltiple (MM) es la gammapatia monoclonal (GM) que más frecuentemente compromete la función renal, no obstante, un número creciente de enfermedades renales asociadas a GM están siendo reconocidas. Las GM son un conjunto de entidades caracterizadas por la producción anómala y secreción a la sangre de una inmunoglobulina (Ig) monoclonal (de un mismo clon de células plasmáticas) o un fragmento de la misma (cadenas pesadas, ligeras o ambas) que puede depositarse en los órganos de forma organizada como cristales, fibrillas o microtúbulos, o de forma no organizada (granular). Esta Ig llega a depositarse principalmente en el riñón, no sólo porque es un órgano muy vascularizado, sino también porque el túbulo renal tiene un papel predominante en el metabolismo de las Igs. El diagnóstico del compromiso renal ha sufrido cambios en las últimas décadas, siendo cada vez más certero debido al desarrollo e implementación rutinaria de distintas técnicas de laboratorio (tinciones con anticuerpos específicos contra cadenas ligeras kappa y lambda, estudio con microscopia electrónica (ME) y el desarrollo de técnicas cada vez más sensibles para detectar el componente monoclonal en sangre u orina). El compromiso renal en estas patologías frecuentemente se asocia a GM malignas, generalmente asociadas a depósitos de cadenas ligeras. Cada vez son más los casos de disfunción renal asociados a GM, y en muchos de estos es evidente el progreso a enfermedad renal terminal y con altas tasas de recurrencia después del transplante renal.

Multiple myeloma (MM) is the monoclonal gammopathy (MG) that most frequently compromises renal function; however, a growing number of renal diseases associated with monoclonal gammopathies are being recognized. Monoclonal gammopathies (MG) are a set of entities characterized by the abnormal production and secretion into the blood of a monoclonal immunoglobulin (Ig) from a single clone of plasma cells or a fragment thereof (heavy, light chains orboth) which can be deposited in the organs in an organized way such as crystals, fibrils or microtubules, orin an unorganized (granular) form. This Ig is mainly deposited in the kidney, not only because it is a very vascularized organ, but also because the renal tubule plays a predominant role in the metabolism of Igs. The diagnosis of renal involvement has undergone changes in the last decades, being more and more certain due to the development and routine implementation of different laboratory techniques (stains with specific antibodies against kappa and lambda light chains, study with electron microscopy (EM), development of increasingly sensitive techniques for detecting the monoclonal component in blood or urine). Renal involvement in these pathologies is often associated with malignant MG, generally associated with light chain deposits. Increasingly, there are cases of renal dysfunction associated with MG, and progression to terminal renal disease and high rates of recurrence after renal transplantation are evident in many of these.

Gammapatía monoclonal de significado incierto A propósito de un caso de nefropatía por depósito de cadenas ligeras lambda / Monoclonal gammopathy of undetermined significance Apropos of a case of lambda light chain deposition nephropathy

La nefropatía asociada a las gammapatías monoclonales es debida principalmente al depósito de cadenas ligeras. Las enfermedades renales paraproteinémicas son lesiones asociadas con depósito de inmunoglobulinas intactas o fragmentos de inmunoglobulinas (cadenas pesadas y cadenas ligeras). La enfermedad por depósito de cadenas ligeras es una condición rara, caracterizada por el depósito de cadenas ligeras monoclonales en muchos órganos y a nivel renal predominantemente en glomérulos y membranas basales tubulares. La enfermedad está frecuentemente asociada con desórdenes linfoproliferativos, y la mayoría de casos son causados por depósito de cadenas ligeras kappa. Aunque se presenta sobre todo en cuadros malignos, en ocasiones no se detecta patología hematológica y se denomina idiopática o "primaria". Suele manifestarse como una insuficiencia renal severa con proteinuria nefrótica, no tiene tratamiento claramente establecido y el pronóstico es malo. Se describen las características clínicas e histológicas del segundo caso informado en Colombia de nefropatía por depósito de cadenas ligeras diagnosticado en el contexto de una enfermedad renal paraproteinémica sin datos de malignidad. (Acta Med Colomb 2014; 39: 196-201).

Nephropathy associated with monoclonal gammopathies is mainly due to light chain deposition. The paraproteinemic kidney diseases are lesions associated with deposition of intact immunoglobulins or fragments of immunoglobulins (heavy and light chains). The disease due to deposition of light chains is a rare condition characterized by deposition of monoclonal light chains in many organs and as for the kidney, predominantly in glomeruli and tubular basement membranes. The disease is frequently associated with lymphoproliferative disorders and the majority of cases are caused by deposition of kappa light chains. Although presented primarily in clinical pictures of malignancy, sometimes no hematological pathology is detected and is called idiopathic or "primary". It usually manifests as severe renal failure with nephrotic proteinuria, has not a clearly established treatment and the prognosis is poor. The clinical and histological features of the second case reported in Colombia of a light chain deposition nephropathy diagnosed in the context of a kidney paraproteinemic disease without malignancy data, is presented. (Acta Med Colomb 2014; 39: 196-201).

A Case of Isolated Light Chain Deposition Disease in the Duodenum

Light chain deposition disease (LCDD) is a rare disorder associated with a clonal proliferation of plasma cells, which synthesize abnormal monoclonal immunoglobulin light chains. LCDD is characterized by systemic deposition of light chains in various organs, with the kidneys being most commonly affected. There have been few reports of isolated LCDD. We report a rare case of LCDD limited to a duodenal polyp. A 63-yr-old man visited our hospital for health screening without symptoms in 2009. On gastrofiberscopy, a duodenal polyp was observed. The biopsy showed diffuse infiltration by atypical plasma cells, which were positive for kappa-type light chains by immunohistochemistry. While the patient refused further management, we could find no evidence of recurrence until 2 yr after the initial diagnosis. It has been reported that isolated LCDD has relatively good prognosis compared to systemic LCDD. However, treatment for this disease has not been established yet.

A Case of Light Chain Deposition Disease Involving Kidney and Bone Marrow with Microangiopathic Hemolytic Anemia / 대한진단검사의학회지

We report a case of light chain deposition disease in a 59-yr-old female showing deposition of monoclonal light chain in the kidney and bone marrow accompanied with a schistocytosis, the morphologic finding of microangiopathic hemolytic anemia. The immunofluorescence examination of the kidney revealed strongly stained kappa-light chain deposits on the glomerular mesangium and capillary wall, tubules, and vessel wall. The electron microscopy demonstrated electron-dense deposits on the glomerular basement membrane and mesangium. Anemia was observed with schistocytosis and Howell-Jolly body in the peripheral blood smears. The immunohistochemical examination of the bone marrow showed the presence of kappa-light chain deposits in scattered plasma cells and thickened vessel wall in the absence of a prominent plasma cell proliferation. Although an immunofixation electrophoresis failed to detect a monoclonal gammopathy, the presence of monoclonal protein could be identified by an abnormal kappa/lambda ratio on the serum free light chain analysis.

A Case of IgA kappa Light Chain Deposition Disease and Combined Adult Fanconi Syndrome with Auer rod-like Intracytoplasmic Inclusions in Plasma Cells and Proximal Renal Tubular Cells / 대한진단검사의학회지

We report a case of IgA kappa light chain deposition disease and combined adult Fanconi syndrome with Auer rod-like intracytoplasmic inclusions in plasma cells and proximal renal tubular cells in a 54-yr-old female. Cytochemical stainings revealed a strong acid phosphatase activity of the inclusions and weak periodic acid-Schiff positivity, whereas the reactions for peroxidase and alpha-naphthyl acetate esterase were negative. An immunostaining verified IgA-kappa inside the plasma cells. Kidney biopsy revealed Bence Jones cast nephropathy with kappa light chain positivity, and Congo red staining was negative. Electron microscopy showed needle-shaped crystals located in tubular epithelial cells.

Clinicopathological Study of Renal Amyloidosis

Study included 13 cases of renal amyloidosis.Oedema, feet and face was the commonest manifestation (100%), two patients (18.18%) also presented with loose motions, ascites and pain in abdomen and one patient had ankylosing spondylitis and cervical spondylitis. On clinical grounds only one case was diagnosed as primary amyloidosis of light chain type, who presented initially with cervical lymphadenopathy and 4 years later with nephrotic syndrome. About 72.72% cases had some chronic disease in the terms of tuberculosis, ankylosing spondylitis, chronic ulcerative colitis, lepromatous leprosy, rheumatoid arthritis and one patient had carcinoma caecum. Congo red stain was positive in both, light chain deposit disease (LCDD) and amyloidosis but polarizing microscope showed mixed birefringence (red, green, yellow) only in amyloidosis. In AFOG and PAS stain, amyloid appeared negative, only peripheral portion revealed blue and pink staining and central area appeared as cutout spaces. Congo red and methyl violet stains and potassium permanganate treatment was not helpful in distinguishing AL amyloidosis from secondary amyloidosis. Hence immunohistochemistry and myeloma profile is a must. It might be possible that in light chain amyloidosis, treatment with methotrexate and prednisolone may improve survival.

A Case of Mesangial Proliferative Glomerulonephritis Presented with Acute Renal Failure in Patients with lambda Light Chain Type-Multiple Myeloma / 대한신장학회잡지

A 44-year-old male was admitted because of nausea and fatigue. At admission, renal insufficiency was disclosed (serum BUN 94 mg/dL, Cr 8.4 mg/ dL). Serum protein electrophoresis was normal. Urine electrophoresis showed non-selective proteinuria with M component in gamma globulin fraction. Serum immunoelectrophoresis disclosed a predominance of free lambda chain protein. Bone marrow aspiration showed a heavy infiltration of immature plasma cells. Percutaneous renal biopsy showed 9 of 10 glomeruli were slightly increased in size. Cellularity and area of mesangium were also increased. Immunohistochemical staining of kappa and lambda light chain was negative. Electron microscopy showed sparse electron dense deposits with no deposition of amyloid-like fibrils in mesangial area. In summary, these finding were compatible with those of mesangial proliferative glomerulonephritis with acute renal failure associated with multiple myeloma (lambda light chain type). There was no published report like this case. Although serum creatinine decreased to 2.1 mg/dL following steroid-pulse therapy, renal function came to deteriorate again after a month of discharge. Permanent hemodialysis was applied.

A Case of Idiopathic Light Chain Deposition Disease / 대한신장학회잡지

Light chain deposition disease (LCDD) is a systemic disorder characterized by the deposition of monoclonal immunoglobulin light chains (LCs) in various organs. As LCs are overproduced by an abnormal clone of B cells, LCDD is usually described in the course of plasma cell dyscrasias or other lymphoproliferative disorders. However, it can occur in the absence of any detectable hematological disorder even during prolonged follow-up. We experienced a case of 62-year-woman who presented generalized edema, massive proteinuria and renal insufficiency. The histologic findings showed nodular glomerular mesangial expansion and prominent ribbon like immunohistochemical staining for kappa-light chain in the glomerular capillary wall. There was no evidence of multiple myeloma in bone marrow biopsy specimen. Because she refused the intensive chemothrapy, low dose of prednisolone and cyclophosphamide were prescribed for 6 months. Her renal function was maintained relatively well without renal replacement therapy for 7 months. We report a case of idiopathic LCDD not associated with multiple myeloma or other plasma cell dysclasia.

A Case of lambda-type Light Chain Deposition Disease Manifested as Acute Renal Failure and Multiple Organ Dysfunction by Embolic Events / 대한신장학회잡지

Light chain deposition disease is caused by systemic paraprotein deposition resulting from monoclonal plasma cell dyscrasia. It is usually characterized rapidly progressive renal failure and multiple organ dysfunctions. Besides deposition of light chain, it can lead to multiple organ dysfunctions due to hyperviscosity syndrome. We experienced a case of 54-year-old man who presented as an acute renal failure, and elevation of liver enzyme. Radiologically, there was no abnormal finding except enlargement of both kidney in abdominal sonogram. Globulinuria was noticed on 24 hrs-urine study. The histologic findings of kidney showed lambda chain deposits in basement membrane of tubules and glomeruli, interstitium, and vessel walls. On 10th day of hospitalization, he developed sudden hypoxia that was not corrected by oxygen supplementation, and focal neurologic signs accompanied with a change of consciousness. We report a case of light chain deposition disease manifested as an acute renal failure and liver enzyme elevation with suspicious multiple organ embolic events later.

A Case of Light Chain Deposition Disease Associated with Renal Amyoidosis / 대한신장학회잡지

Light chain deposition disease of kidney is characterized by deposition of monoclonal immunoglobulin light chain and electron-dense material in glomerular and tubular basement membrane and usually associated with multiple myeloma or other plasma cell dyscrasia. With light chain deposition disease affecting kidney, three clinical patterns have been recognized; nephrotic syndrome, rapidly progressive renal failure and slowly progressing chronic renal failure. The majority of patients present proteinuria and renal insufficiency. Cytotoxic therapy has been considered as treatment of choice. Favorable effect of melphalan given together with prednisone has been reported in a few cases. A 64-year-old male was admitted with generalized edema and exertional dyspnea, and was presumptively diagnosed as congestive heart failure and hypertension. He also presented increased serum creatinine and nephrotic range proteinuria. Urine protein electrophoresis and urine and serum immunoelectrophoresis revealed monoclonal gammopathy of IgG kappa type. Work up for multiple myeloma including bone marrow biopsy showed results compatible with smoldering myeloma. Renal biopsy showed findings of light chain deposition disease and Congo-red positive amyloidosis. After we treated the patient with melphalan and predinsone for two cycles, amount of proteinuria and serum creatinine were decreased.