Una causa olvidada de insuficiencia cardíaca / A forgotten cause of heart failure

Amyloidosis is a low-frequency disease that can cause compromise of different systems. We report a case of heart failure in an 81-year-old woman secondary to amyloidosis, in which the echocardiogram was a valuable diagnostic tool.

Serum free light chain level in patients with diabetic kidney disease and its correlation with renal function indexes / 中国医师进修杂志

Objective:To explore the correlation between the level of serum free light chain and renal function indexes in patients with diabetic kidney disease (DKD).Methods:The clinical data of 120 patients with DKD (study group) and 80 patients with simple diabetes (diabetes group) in the Beijing Sixth Hospital from October 2017 to October 2020 were retrospectively analyzed. Five ml of fasting peripheral venous blood were collected, the levels of serum uric acid, creatinine, homocysteine (Hcy) and free light chain (including free light chain κ, free light chain λ, ratio of free light chain κ and free light chain λ and total free light chain) were detected, and the estimated glomerular filtration rate (eGFR) was calculated. The correlation between total free light chain and renal function indexes in patients with DKD was analysis by Pearson method.Results:The free light chain κ, free light chain λ, ratio of free light chain κ and free light chain λ, total free light chain, uric acid, creatinine and Hcy in DKD group were significantly higher than those in diabetes group: (33.92 ± 9.06) mg/L vs. (17.65 ± 4.72) mg/L, (17.52 ± 2.83) mg/L vs. (9.81 ± 3.20) mg/L, 1.93 ± 0.23 vs. 1.80 ± 0.25, (51.44 ± 12.31) mg/L vs. (27.46 ± 7.92) mg/L, (383.69 ± 96.11) μmol/L vs. (345.93 ± 93.94) μmol/L, (117.57 ± 22.39) μmol/L vs. (75.06 ± 14.73) μmol/L and (17.64 ± 5.76) μmol/L vs. (11.66 ± 5.46) μmol/L, the eGFR was significantly lower than that in diabetes group: (103.95 ± 22.58) ml/(min·1.73 m 2) vs. (142.65 ± 26.50) ml/(min·1.73 m 2), and there were statistical differences ( P<0.01). Pearson correlation analysis results showed that serum total free light chain in patients with DKD was positively correlated with uric acid, creatinine and Hcy ( r = 0.707, 0.709 and 0.820; P<0.01), and negatively correlated with eGFR ( r = -0.730, P<0.01). Conclusions:The expression level of serum free light chain is obviously increased in patients with DKD, it has a certain correlation with renal function indexes. It can be used as one of the evaluation indicators for disease monitoring.

Perfil Clínico, Laboratorial e de Métodos de Imagem na Amiloidose Sistêmica em um Centro de Referência Cardiológico Brasileiro / Clinical, Laboratory, and Imaging Profile in Patients with Systemic Amyloidosis in a Brazilian Cardiology Referral Center

Resumo Fundamento Amiloidose sistêmica é uma doença com manifestações clínicas diversas. O diagnóstico envolve suspeita clínica, aliada a métodos complementares. Objetivo Descrever o perfil clínico, laboratorial, eletrocardiográfico e de imagem no acometimento cardíaco da amiloidose sistêmica. Métodos Estudo de uma amostra de conveniência, analisando dados clínicos, laboratoriais, eletrocardiográficos, ecocardiográficos, medicina nuclear e ressonância magnética. Considerou-se significância estatística quando p < 0,05. Resultados Avaliaram-se 105 pacientes (com mediana de idade de 66 anos), sendo 62 homens, dos quais 83 indivíduos apresentavam amiloidose por transtirretina (ATTR) e 22 amiloidose por cadeia leve (AL). Na ATTR, 68,7% eram de caráter hereditário (ATTRh) e 31,3% do tipo selvagem (ATTRw). As mutações mais prevalentes foram Val142Ile (45,6%) e Val50Met (40,3%). O tempo de início dos sintomas ao diagnóstico foi 0,54 e 2,15 anos nas formas AL e ATTR (p < 0,001), respectivamente. O acometimento cardíaco foi observado em 77,9% dos ATTR e 90,9% dos AL. Observaram-se alterações de condução atrioventricular em 20% e intraventricular em 27,6% dos pacientes, sendo 33,7 % na ATTR e 4,5% das AL (p = 0,006). A forma ATTRw apresentou mais arritmias atriais que os ATTRh (61,5% x 22,8%; p = 0,001). Ao ecocardiograma a mediana da espessura do septo na ATTRw x ATTRh x AL foi de 15 mm x 12 mm x 11 mm (p = 0,193). Observou-se BNP elevado em 89,5% dos indivíduos (mediana 249 ng/mL, IQR 597,7) e elevação da troponina em 43,2%. Conclusão Foi possível caracterizar, em nosso meio, o acometimento cardíaco na amiloidose sistêmica, em seus diferentes subtipos, através da história clínica e dos métodos diagnósticos descritos.

Abstract Background Systemic amyloidosis is a disease with heterogeneous clinical manifestations. Diagnosis depends on clinical suspicion combined with specific complementary methods. Objective To describe the clinical, laboratory, electrocardiographic, and imaging profile in patients with systemic amyloidosis with cardiac involvement. Methods This study was conducted with a convenience sample, analyzing clinical, laboratory, electrocardiographic, echocardiographic, nuclear medicine, and magnetic resonance data. Statistical significance was set at p < 0.05. Results A total of 105 patients were evaluated (median age of 66 years), 62 of whom were male. Of all patients, 83 had transthyretin (ATTR) amyloidosis, and 22 had light chain (AL) amyloidosis. With respect to ATTR cases, 68.7% were the hereditary form (ATTRh), and 31.3% were wild type (ATTRw). The most prevalent mutations were Val142Ile (45.6%) and Val50Met (40.3%). Time from onset of symptoms to diagnosis was 0.54 and 2.15 years, in the AL and ATTR forms, respectively (p < 0.001). Cardiac involvement was observed in 77.9% of patients with ATTR and in 90.9% of those with AL. Alterations were observed in atrioventricular and intraventricular conduction in 20% and 27.6% of patients, respectively, with 33.7% in ATTR and 4.5% in AL (p = 0.006). In the ATTRw form, there were more atrial arrhythmias than in ATTRh (61.5% versus 22.8%; p = 0.001). On echocardiogram, median septum thickness in ATTRw, ATTRh, and AL was 15 mm, 12 mm, and 11 mm, respectively (p = 0.193). Elevated BNP was observed in 89.5% of patients (median 249, ICR 597.7), and elevated troponin was observed in 43.2%. Conclusion In this setting, it was possible to characterize cardiac involvement in systemic amyloidosis in its different subtypes by means of clinical history and the diagnostic methods described.

Advances in the application of nuclear medicine imaging in the diagnosis and treatment of systematic light chain amyloidosis / 中华核医学与分子影像杂志

Systematic light chain (AL) amyloidosis is the most common forms of amyloidosis, which manifests as multiple organ system involvement, rapid progress, dire prognosis, difficult therapy and high mortality. Many patients may miss the optimal treatment as a result of not being diagnosed timely. Therefore, early diagnosis and assessment of involved extent of AL are clinical focuses. Related clinical studies have demonstrated that nuclear medicine imaging can be non-invasive in detecting amyloid deposits. It can not only early assess the extent and distribution of amyloid deposits in systemic AL amyloidosis, but also offer the indications for risk stratification, treatment response monitoring and prognosis assessment of the patients, especially for positron amyloidosis-specific tracers, which may have great prospects in the future. This review summarizes the application of nuclear medicine imaging in the systematic AL amyloidosis.

Daratumumab for the treatment of primary systemic amyloidosis: a multicenter retrospective analysis / 中华内科杂志

Objective:To analyze the efficacy and safety of Daratumumab for the treatment of primary AL light chain systemic amyloidosis.Methods:Twenty one patients who were diagnosed as primary AL light chain systemic amyloidosis and treated with Daratumumab from 7 centers were retrospectively analyzed. Daratumumab was administrated as first line therapy in seven patients and 14 patients with relapsed settings. Hematological response, safety and survival were analyzed.Results:All 7 patients achieved very good partial response (VGPR) or better with first-line application of daratumumab. Three patients died, and the other four achieved organ remission. Among 14 relapsed patients, 2 patients had a difference of free light chain (dFLC) less than 20 mg/L before treatment, and 9 with a dFLC of more than 50 mg/L. All patients reached partial response (PR) or better, including 4 patients with complete response (CR), 3 with VGPR and 2 with PR. The response rate was 100% in 3 patients with dFLC 20-50 mg/L at baseline. The organ remission rate was 50% in patients with heart involvement and 58.3% in patients with kidney impairment. The overall median follow-up period was 5.3 months, and 11 months in surviving patients. One patient died of severe infection and disseminated intravascular coagulation (DIC) with stable amyloidosis. One patient switched to other regimens because dFLC elevated but did not fulfill progressive disease after 2 year application. As to safety, no grade 3/4 infusion reaction developed, and grade 1 infusion reaction occurred in 3 cases during the first infusion. Lymphocytopenia was seen in 75% patients including grade 3 or more in 30% patients.Conclusion:Daratumumab is effective to eliminate serum free light chain in both newly diagnosed and relapsed patients with systemic amyloidosis.

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.

Renal tubular P-glycoprotein expression is reduced in plasma cell disorders

BACKGROUND: P-glycoprotein (P-gp) transports many chemicals that vary greatly in their structure and function. It is normally expressed in renal proximal tubular cells. We hypothesized that P-gp expression influences light chain excretion. Therefore, we investigated whether renal tubular P-gp expression is altered in patients with plasma cell disorders. METHODS: We evaluated renal biopsy specimens from patients with plasma cell disorders (n = 16) and primary focal segmental glomerulosclerosis (the control group, n = 17). Biopsies were stained with an anti-P-gp antibody. Loss of P-gp expression was determined semi-quantitatively. Groups were compared for loss of P-gp expression, and clinical variables. RESULTS: P-gp expression loss was more severe in patients with plasma cell disorders than it was in those with glomerulonephritis (P = 0.021). In contrast, clinical and histological parameters including serum creatinine, level of urinary protein excretion, and interstitial fibrosis/tubular atrophy grade were not significantly different between the groups. P-gp expression loss increased with age in patients with plasma cell disorders (P = 0.071). This expression loss was not associated with serum creatinine, the level of urinary protein excretion or the interstitial fibrosis/tubular atrophy grade. There was no significant association between the severity of P-gp expression loss with the types and serum levels of light chains, isotypes and serum immunoglobulin levels. CONCLUSION: Renal tubular P-gp expression is significantly down-regulated in patients with plasma cell disorders characterized by nephrotic range proteinuria. Additional studies are needed to determine whether reintroduction of renal tubular P-gp expression would mitigate the proximal tubular injury that is caused by free-light chains.

The value of serum heavy/light chain immunoassay to assess therapeutic response in patients with multiple myeloma / 中华血液学杂志

Objective@#To assess the value of immunoglobulin heavy/light chain (HLC) immunoassay on therapeutic response in patients with multiple myeloma(MM).@*Methods@#A total of 45 newly diagnosed MM patients were retrospectively enrolled in Peking Union Medical College Hospital from 2013 to 2016, whose 115 serum samples were consecutively collected. HLC was tested to evaluate response and compare with other methods for M protein detection.@*Results@#①There were 30 males and 15 females in total of whom the monoclonal immunoglobulin was IgG in 27 (IgGκ∶IgGλ 12∶15) and IgA (IgAκ∶IgAλ 9∶9) in 18. The arerage age of the studied population was 59 (range 43-80) . ② In 34 patients with serum sample at diagnosis, 32 (94.1%) had abnormal HLC ratio (rHLC) while 2 patients with IgG had normal rHLC. The percentages of abnormal rHLC was 81.8% (18/22) at partial response、50.0%(9/18) at very good complete response and 16.0%(4/25) at complete response. ③In 25 patients reaching CR, there were 13 with IgG and 12 with IgA. 4 patients equally split of IgG and IgA had abnormal rHLC at complete response. ④By monitoring the rHLC of some patients consecutively, we found that the remission of rHLC was to some extent behind the remission of SPE and IEF, or even rFLC.@*Conclusion@#Immunoglobulin HLC detection is one feasible method for minimal residual disease detection.

Classification of cardiac amyloidosis: an immunohistochemical analysis / 中华病理学杂志

Objective@#To evaluate the sensitivity and specificity of immunohistochemistry (IHC) in the classification of cardiac amyloidosis on endomyocardial biopsy (EMB) and heart allograft.@*Methods@#Twenty cardiac tissues from 19 patients at Fuwai Hospital from January, 1990 to April, 2017 with histopathologic features of amyloidosis and Congo red staining positivity were included. IHC was performed with monoclonal antibodies against AA amyloid and polyclonal antibodies against transthyretin (ATTR), λ-light chain (AL-λ), κ-light chain (AL-κ), ApoAⅠ, ApoAⅡ, ApoA Ⅳ and β2-microglobin. The extent of interstitial staining was evaluated by light microscopy, and three patterns were recognized; these included diffuse pericellular pattern, discrete pericellular pattern, and nodular pattern. Two patterns of vascular deposition were also noted, including arterial pattern and venous pattern. Endocardial involvement was also assessed and recorded.@*Results@#Nineteen cases were divided into three groups according to the pattern of proteins expression in specimens. The first group (5 cases) only showed single protein expression on EMB. The second group (6 cases) showed more than one protein expression, but one of them was intensely stained or any staining of any protein together with ApoA Ⅳ co-staining. The third group (8 cases) also showed more than one protein expression and all of them had intense staining. Amyloid deposits were successfully subtyped as AL-λ, ATTR, AL-κ and ApoAⅠby IHC in the former two groups with the sensitivity of 11/19. In the third group, amyloid deposits could not be subtyped by immunohistochemistry due to their poor specificity. The pericellular pattern tended to favor AL over ATTR amyloidosis and vascular deposition tended to favor ATTR.@*Conclusions@#Amyloid deposits can be reliably subtyped in diagnostic cardiac specimens using IHC. The co-deposition of chaperon proteins, the distribution of amyloid proteins and clinical features are also auxiliary to subtype cardiac amyloidosis.

Primary systemic amyloidosis with chronic diarrhea onset: report of one case and review of literature / 白血病·淋巴瘤

Objective To explore the clinical features, diagnosis and treatment of chronic diarrhea with primary systemic amyloidosis (AL). Methods The clinical experience of an AL patient with chronic diarrhea who was admitted to chinese PLA General Hospital in November 2017 was presented, and the related literature was reviewed. Results The patient was definitely diagnosed as AL with chronic diarrhea onset;after treatment with VCD regimen, the condition was improved obviously and achieved complete remission. Conclusion AL patient with chronic diarrhea onset needs to undergo various detections to make a clear diagnosis and differential diagnosis, and the bortezomib-based treatment scheme can achieve good curative effect.

Solitary ulcerated plaque on the face - an unusual presentation of cutaneous plasmacytosis?

Abstract Cutaneous and systemic plasmacytosis is a rare disorder characterized by cutaneous polyclonal plasma cell infiltration frequently associated with polyclonal hypergammaglobulinemia and lymphadenopathy. We report a case of a 67-year-old woman with an inflammatory ulcerated plaque in the left masseter region. A skin biopsy showed dense perivascular infiltrate of mature plasma cells in the dermis without atypia and immunoglobulin light chain restriction. After physical examination and further investigation, we ruled out systemic disease. Our patient was successfully treated only with hydrocortisone cream application. Few cases of isolated benign primary cutaneous plasmacytosis have been described, particularly in children. After excluding the diagnosis of a reactive process to an infection, which is unlikely in this case, we suspected of a rare manifestation of primary cutaneous plasmacytosis in adults with distinct presentation and clinical course.

The clinical and laboratory features of IgG-2κ light chain multiple myeloma: analysis of three cases / 白血病·淋巴瘤

Objective To investigate the clinical and laboratory features of IgG-2κ light chain multiple myeloma. Methods The clinical data and laboratory results of 2 multiple myeloma (MM) patients with IgG-2κ light chain were analyzed and the related literatures were reviewed. Results Two male and 1 female patients were 50-82 years old and mainly suffered with backache, infection, anemia and renal dysfunction. Multiple osteolytic bone destruction was detected in X-ray as well as magnetic resonance imaging (MRI). The level of serum IgG was normal, slight or obviously increased, but the levels of IgA and IgM were decreased. The levels of κ light chain in serum and urine were both increased significantly, and Bence-Jones protein was positive. Double M protein peaks of serum in γ area were detected by protein electrophoresis in 2 patients. A single band of IgG and double bands of light chain κ were revealed by immunofixation electrophoresis. Bone marrow smear showed that abnormal plasma cells were increased obviously. One patient gave up chemotherapy because of lung infection, acute left heart failure and acute renal failure, the others 2 patients achieved partial remission and stable disease by receiving DVD and VAD chemotherapy. Conclusions IgG-2κ light chain MM lacks typical clinical presentation, but some laboratory characteristics may be different from those of IgG-κ light chain. Further researches are needed to confirm whether or not it belongs to biclonal MM.

Analysis of clinical and pathological manifestations of light chain proximal tubulopathy / 中华肾脏病杂志

Objective To investigate the clinical and pathological characteristics of light chain proximal tubulopathy (LCPT).Methods Nine patients with LCPT diagnosed by renal biopsy in Peking University First Hospital from January 1,2011 to September 30,2016 were enrolled,and their clinical findings and pathological features were reviewed.Immunofluorescence (IF) of light chains (κ,λ) on paraffin sections after protease digestion and immunogold labeling of light chains (κ,λ) on ultrathin sections were performed in some cases.Results The main clinical manifestation of the nine patients was proteinuria of small molecules,with acute or chronic renal insufficiency,and six of them led to partial or complete Fanconi syndrome (FS).The hematologic diseases included 3 cases of multiple myeloma and 6 cases of monoclonal gammopathy of renal significance (MGRS).Pathological examination of renal biopsy showed two types:crystalline and noncrystalline LCPT.Seven cases of crystalline LCPT were stained for κ light chain,the proximal tubular epithelial cytoplasm exhibited fine granular vacuolation,with needle-shaped crystals and clear clefts by light microscopy,the intracytoplasmic inclusions of various shapes including rhomboidal,rectangular and rod-shaped crystals were identified by electron microscopy.Two cases of noncrystalline LCPT were stained for λ light chain,the prominent argyrophilic granules in cytoplasm of proximal tubular epithelia were observed by light microscopy,and intracytoplasmic large and irregular shaped phagolysosomes were found by electron microscopy,cast nephropathy were coexisted in these 2 cases,the additional light chain deposition disease were confirmed in one of them by electron microscopy and IF.All cases had monotypic staining of light chains in cytoplasm of proximal tubules by IF on frozen tissue and paraffin sections after protease digestion,with the latter method being more sensitive than the routine IF.The immunogold labeling showed specific monotypic labeling of κ and λ light chain on intracytoplasmic crystals and phagolysosomes respectively by immunoelectron microscopy.Conclusions LCPT is a rarely reported entity that manifested as acquired Fanconi syndrome and dysfunction of proximal tubules clinically.Pathologically it is divided into two types:crystalline and noncrystalline LCPT,with more prevalent of κ light chain related crystalline type,noncrystalline LCPT is mostly λ type,and is easily coexisted with cast nephropathy.The IF and immunoelectron microscopy of light chains(κ,λ) and ultrastructural examination by electron microscopy are important methods for the diagnosis of LCPT.

Treatment of idiopathic light chain deposition disease: complete remission with bortezomib and dexamethasone / Tratamento da doença de depósito de cadeia leve idiopática: remissão completa com bortezomib e dexametasona

Abstract Light chain deposition disease (LCDD) is a rare clinical entity characterized by the deposition of light chain immunoglobulins in different tissues and primarily affects the kidneys, followed by the liver and heart. This disease often manifests as nephrotic syndrome with marked proteinuria and rapid deterioration of renal function. More than 50% of cases are secondary to multiple myeloma or other lymphoproliferative diseases, with a well-established treatment aimed at controlling the underlying disease. In rare cases, there is no detection of an associated hematological disease, referred to as idiopathic LCDD. In these cases, there is no evidence-based consensus on the therapeutic approach, and management is based on the clinical experience of reported cases. Here we report a case of idiopathic LCDD treated with bortezomib and dexamethasone with complete hematologic responses, significant reduction of proteinuria, and improved renal function.

Resumo A doença de deposição de cadeia leve (DDCL) é uma entidade clínica rara caracterizada pela deposição de cadeias leves das imunoglobulinas em diferentes tecidos e afeta principalmente os rins, seguido pelo fígado e coração. Manifesta-se frequentemente como síndrome nefrótica com proteinúria marcante e rápida deterioração da função renal. Mais de 50% dos casos são secundários ao mieloma múltiplo ou outras doenças linfoproliferativas, tendo seu tratamento bem estabelecido, voltado para o controle da doença de base. Em casos raros, não há detecção de uma doença hematológica associada, sendo referida como DDCL idiopática. Nestes casos, não há um consenso baseado em evidências sobre a abordagem terapêutica, tendo sua conduta baseada na experiência clínica dos casos relatados. Aqui, nós relatamos um caso de DDCL idiopática tratado com bortezomib e dexametasona atingindo resposta hematológica completa, redução significativa da proteinúria e recuperação da função renal.

The significance of serum light chain ratio in the diagnosis of multiple myeloma and primary nephritic / 中国医师杂志

Objective To explore the clinical value of serum κ/λ ratio in the differential diagnosis of multiple myeloma (MM) and primary nephritic,and to explore its relationship with MM other laboratory markers.Methods We obtained 88 cases of MM patients with serotyping by immunofixation and 109 cases of primary nephritic patients.In accordance with the composition of protein M in immunofixation electrophoersis (IFE),88 patients were divided into 4 groups:IgGκ,IgGλ,IgAκ and IgAλ.In addition,45 serum samples of health examination were collected as control samples.The levels of serum IgG,IgA,IgM,light chain κ and λ in each group were tested by immune turbidimetry,and κ/λ ratio was calculated.The levels of serum β2-microglobin (β2-MG),albumin (ALB),serum urea (BUN),creatinine (CRE),and M protein percentage were also detected.Results (1) In MM group,there was no significant difference of sex and International Staging System (ISS) stages between each type(P ＞ 0.05),while there was significant difference in age distribution between each type (P ＜ 0.05).(2) Compared to control,the levels of se-rum light chain κ,κ/λ ratio,and matched Ig were significantly higher and the level of light chain λ and other Ig were significantly lower in κ typed MM patients,while the levels of serum light chain λ were significantly higher and the levels of serum light chain κ,and κ/λ ratio were significantly lower in λ typed MM patients(P ＜0.01).The levels of light chain κ,λ,and IgG in primary nephritic patients were significantly lower than control(P ＜0.01),while there was no significant difference in κ/λ ratio between two group (P ＞ 0.05).There were also significant difference of light chain,Ig,BUN and CRE levels between MM patients and primary nephritic patients (P ＜ 0.05).(3) The κ/λ ratio correlated with serum ALB (r =-0.264,P =0.013) and β2-MG (r =0.235,P =0.040) levels in MM.Conclusions Serum levels of light chain κ,λ,and κ/λ ratio have great significance in the differential diagnosis of multiple myeloma and primary nephritic.The κ/λ ratio correlated with several tumor markers in MM progresses,rendering it as a promising method for diagnosis and prognosis monitoring of MM.

De Novo AL Amyloidosis in a Renal Allograft / 대한내과학회지

Amyloidosis is characterized by the extracellular deposition of amyloid in various tissues and organs, particularly the kidney and heart. The estimated incidence of systemic amyloidosis is at least 8 per million population per year. However, few cases of systemic amyloidosis in renal allografts have been reported. A stable renal transplant recipient was admitted with proteinuria and dyspnea on exertion. The M-peak was found on serum and urine protein electrophoresis, and lambda (λ) dominance was confirmed by serum and urine free-light-chain test. The patient was diagnosed with systemic amyloidosis of a renal allograft, by allograft biopsy, at 22 years after renal transplantation. We report a case of AL amyloidosis in a stable renal allograft and review the medical literature.

A Case of Light Chain Deposition Disease in a Patient with Diabetes and Nodular Glomerulosclerosis / 대한내과학회지

A 50 year-old male with a 10-year history of diabetes was admitted to the hospital for edema and foamy urine. At the time of admission, serum creatinine was 1.99 mg/dL and 24 h urine protein levels were 4.0 g/day. Renal biopsy showed nodular glomerulosclerosis. Immunofluorescence demonstrated the presence of kappa light chains along the glomerular and tubular basement membrane. Electron microscopy showed granular electron-dense deposits along the glomerular subendothelium and tubular basement membrane. Serum protein electrophoresis was negative for a monoclonal spike; however, urine protein electrophoresis demonstrated a monoclonal spike. Bone marrow examination was compatible with multiple myeloma and the patient was diagnosed with light-chain deposition disease associated with multiple myeloma. This report stresses the significant challenges that occur when diagnosing light-chain deposition disease in kidneys of patients with long standing diabetes, and discusses previously reported cases of light-chain deposition disease in Korea.

Utilidad del ensayo de cadenas livianas libres en suero en el manejo de gammapatías monoclonales: diagnóstico, pronóstico y monitoreo / Usefulness of serum free light chain testing in the handling of monoclonal gammapathies: diagnosis, prognosis and monitoring

El ensayo de cadenas livianas libres en suero cuantifica los niveles de κ y λ libres. Existen tres indicaciones principales para la medición de cadenas livianas libres en el manejo de pacientes con mieloma múltiple y enfermedades relacionadas. Primero, en el contexto del diagnóstico, donde en combinación con la electroforesis de proteínas en suero y la inmunofijación en suero proporcionan el esquema de tamizaje de mayor sensibilidad, eliminando la necesidad de analizar la orina de 24 horas. Segundo, los valores basales de cadenas livianas libres en suero han mostrado tener valor pronóstico para la mayoría de las gammapatías monoclonales. Tercero, el ensayo de cadenas livianas libres en suero permite un monitoreo cuantitativo y sensible en pacientes con presentación oligosecretora de la enfermedad, incluyendo la AL amiloidosis y cerca del 70% de los pacientes históricamente denominados no secretores. Esta revisión tiene por objeto actualizar la información sobre las aplicaciones de esta importante prueba...

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

Idiopathic Light Chain disease (ILCD) is a systemic disease characterized by a deposit in different organs of light chain monoclonal immunoglobulins, produced by an abnormal clone ofB cells. It is usually found in the course ofa plasma cell dyscrasia and in other lymphoproliferative alterations; however it may occur in absence of any hematologic disease and is denominated as idiopathic. We report a 51-year-old mole admitted to the hospital due to anasarca. Laboratory evaluation showed a serum creatinine of 1.4 mg/dl, a serum albumin of1.6 g/dl, a serum cholesterol of 687 mg/dl and a proteinuria of 5.3 g/day Light chains with a predominance of a monoclonal component were identified in urinary proteins by electrophoresis and kappa chains were identified by immunofixation. A renal biopsy showed a diffuse nodular glomerulopathy with a 35% tubular atrophy and interstitial sclerosis. Electrón microscopy confirmed light chain deposition. The bone marrow biopsy showed a myeloid hyperplasia. Thepatient was initially treated with methylprednisolone and plasmapheresis with a reduction in serum creatinine and disappearance of urinary kappa component. Albuminuriapersisted and a malnutrition-inflammatory complex syndrome was diagnosed. Hemodialysis with ultrafiltration was started along with cyclophosphamide. Thepatient receivedhemodialysisforsixmonths and continued with methylprednisolone.

The clinical significance of serum free light chain in primary systemic amyloidosis / 中华内科杂志

Objective To evaluate the diagnostic and therapeutic significance of serum free light chain (sFLC) in primary systemic(AL) amyloidosis. Methods Twenty-five patients with AL amyloidosis,including 18 men and 7 women with a mean age of 54(47-77) years old, were enrolled from October, 2005to May, 2010. sFLC was measured by immunoturbidimetric assay. The type of monoclonal light chain was judged upon sFLC κ/λ and its sensibility was compared with serum immunofixation and immunohistochemical analysis. Four patients were treated with M (T)D (melphalan/thalidomideand, dexamethasone), one with VD (velcade and dexamethasone) and four with high-dose melphalan followed by autologous stem cell support. The changes of sFLC were serially determined before and after treatment. Results Among the 25 patients with AL amyloidosis, two were κ light chains of precursor protein and 23 were λ light chains. Mean plasma cell in bone marrow was 3.5% (0-15%). Nineteen (76%) patients had abnormal elevated sFLC and abnormal κ/λ ratios, and 17(68% ) patients with immunofixation positive. The sFLC test had similar sensitivity as serum immunofixation (P = 0. 727 ). Twenty-one (84%) patients were shown to have either κor λ immunoreactive amyloid deposits on biopsied tissues. The sFLC test combined with serum immunofixation allowed the M protein to be detected in 22 (88%) patients. The positive rates of immunohistochemical analysis combined with sFLC test and/or serum immunofixation were 96%. Four patients with hematologic response showed obvious improvement in visceral organ involvement, but illness of 5 patients without hematologic response kept stable or progressed. Conclusions sFLC test is a sensitive qualitative and quantitative method to detect M protein. Preliminary data show the patients with obvious sFLC level decrease and/or κ/λ recovery to normal may have a high percentage of improved organs function. sFLC is critical index in diagnosing AL amyloidosis, which might help efficacy assessment.