Renal amyloidosis: a new time for a complete diagnosis

Amyloidoses are a group of disorders in which soluble proteins aggregate and deposit extracellularly in tissues as insoluble fibrils, causing organ dysfunction. Clinical management depends on the subtype of the protein deposited and the affected organs. Systemic amyloidosis may stem from anomalous proteins, such as immunoglobulin light chains or serum amyloid proteins in chronic inflammation or may arise from hereditary disorders. Hereditary amyloidosis consists of a group of rare conditions that do not respond to chemotherapy, hence the identification of the amyloid subtype is essential for diagnosis, prognosis, and treatment. The kidney is the organ most frequently involved in systemic amyloidosis. Renal amyloidosis is characterized by acellular pathologic Congo red-positive deposition of amyloid fibrils in glomeruli, vessels, and/or interstitium. This disease manifests with heavy proteinuria, nephrotic syndrome, and progression to end-stage kidney failure. In some situations, it is not possible to identify the amyloid subtype using immunodetection methods, so the diagnosis remains indeterminate. In cases where hereditary amyloidosis is suspected or cannot be excluded, genetic testing should be considered. Of note, laser microdissection/mass spectrometry is currently the gold standard for accurate diagnosis of amyloidosis, especially in inconclusive cases. This article reviews the clinical manifestations and the current diagnostic landscape of renal amyloidosis.

Secondary Renal Amyloidosis in Rheumatoid Arthritis Patient

@#INTRODUCTION: Rheumatoid arthritis (RA) is one of systemic chronic progressive inflammatory disorders based on immunological disharmonies. Poorly controlled systemic inflammation in RA often leads to renal diseases such as secondary amyloidosis. CASE PRESENTATION: A 30-year-old man complained of swelling and tenderness of multiple joints gradually worsened the past 7 years. His laboratory examination showed anemia, positive rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA). C-reactive protein (CRP) was 48.7 mg/L (Normal value is <5 mg/L), increase in serum creatinine and protein was +3 in urine. His estimated glomerular filtration rate (e-GFR) was 58.3 mL/min/1.73 m2 Radiologic examinations of joints revealed features that support the diagnosis of rheumatoid arthritis. Renal biopsy was done revealed amyloid deposit. He was diagnosed with rheumatoid arthritis and secondary renal amyloidosis. CONCLUSION: Early proper diagnosis of RA is important and immunosuppressive drugs might slow disease progression by controlling the inflammatory process We discussed the importance of early diagnosis and the use of better treatment in managing RA to prevent renal amyloidosis.

A Pediatric Case of Inflammatory Bowel Disease with Renal Amyloidosis

Amyloidosis is a rare disease that results from the deposition of extracellular protein in various body tissues, causing progressive organ dysfunction. Secondary renal amyloidosis is a rare but serious complication of chronic inflammatory bowel disease, particularly in patients with Crohn's disease or ulcerative colitis. We report a case of secondary renal amyloidosis in a pediatric patient who reported a 16-year history of “very early onset inflammatory bowel disease”. Intensive treatment including repeated infliximab infusions improved clinical parameters of inflammatory bowel disease, although renal dysfunction showed progression. Amyloidosis should be considered in patients with IBD, particularly if they suffered disease progression.

Cutaneous and Systemic Plasmacytosis Associated with Renal Amyloidosis

Cutaneous and systemic plasmacytosis (CSP) is a rare disorder of unknown etiology characterized by cutaneous polyclonal plasma cell infiltrates associated with various extracutaneous involvement and polyclonal hypergammaglobulinemia. Here, we report on a 54-year-old male patient with chronic renal insufficiency who presented with disseminated reddish-brown macules and plaques on the face and trunk. In our evaluation, he was found to have lymphadenopathy, polyclonal hypergammaglobulinemia; benign plasma cell infiltration involving the skin, bone marrow, and retroperitoneal area; and renal amyloidosis. To the best of our knowledge, this is the first reported case of CSP associated with renal amyloidosis.

Amiloidose renal secundária ao mieloma múltiplo: relato de caso / Renal amyloidosis caused by multiple myeloma: case report

JUSTIFICATIVA E OBJETIVOS: O mieloma múltiplo (MM) é uma neoplasia maligna grave da medula óssea que ocorre principalmente em pessoas idosas, ocasionalmente complicado por amiloidose. O objetivo deste estudo foi relatar um caso de mieloma múltiplo com amiloidose renal. RELATO DO CASO: Paciente do sexo feminino, 58 anos, apresentou edema, proteinúria (1,5 g/dia), dor lombar e disfunção renal (creatinina sérica de 3,5 mg/dL, depuração de creatinina de 23,4 mL/min/1,73m2), hipercalcemia (cálcio = 10,7 mg/dL), anemia (hemoglobina = 6,7 g/dL), pesquisa de proteínas urinárias de Bence Jones positiva. Radiografias revelaram lesões líticas ósseas. A biópsia renal evidenciou depósitos hialinos (amiloide)no interstício renal e nos glomérulos. Análise de aspirado de medula óssea mostrou proliferação clonal de plasmócitos. Tratada com nifedipina (40 mg/dia), furosemida (40 mg/dia), eritropoetina (8.000 U/semana), ácido fólico (5 mg/dia), carbonato de cálcio (1,5 g/dia), quimioterapia (prednisolona, melfalan, dexametasona,talidomida, vincristina, doxorrubicina) e radioterapia localizada. A evolução mostrou regressão do edema, a função renal ficou estável e ocorreu remissão dos sintomas clínicos durante oito anos. CONCLUSÃO: Relatou-se um caso de mieloma múltiplo complicado com amiloidose. Aspectos sobre o diagnóstico e o tratamentoforam revisados.

BACKGROUND AND OBJECTIVES: Multiple myeloma (MM) is a serious malignant neoplasm of bone marrow, and mostly occurs in the elderly persons. It is occasionally complicated by amyloidosis. The objective of this study was report a case of multiple myeloma with amyloidosis.CASE REPORT: Female patient, 58 year-old, had edema, proteinuria (1.5 g/day), lumbar pain and renal dysfunction (at admission her renal function was noticed to be abnormal, serum creatinine of 3.5 mg/dL; creatinine clearance of 23.4 mL/min/1.73m2), hypercalcemia (calcium = 10.7 mg/dL), anemia(hemoglobin level 6.7 g/dL), urinary Bence Jones protein positive.Skeletal radiographs revealed lytic lesions. Renal biopsy revealed hyaline deposits (amyloid) in the renal interstitium and the glomeruli. Bone marrow aspirate analysis revealed clonal plasma cells. Treated by nifedipine (40 mg/day), furosemide (40 mg/day), erythropoietin (8,000 U/week), folic acid (5 mg/day),calcium carbonate (1.5 g/day), chemotherapy (prednisolone,melphalan, dexametasona, vincristine, thalidomide, doxorubicin)and located radiotherapy. Follow-up showed regression of edema, stable renal function and remission of clinical symptoms during eight years.CONCLUSION: We report a case of multiple myeloma complicated by amyloidosis. Features about the diagnosis and treatment were revised.

Terapia com anti-TNF na amiloidose renal em artrite reumatoide refratária: uma nova perspectiva terapêutica / Anti-TNF therapy in renal amyloidosis in refractory rheumatoid arthritis: a new therapeutic perspective

As amiloidoses são um grupo heterogêneo de doenças caracterizadas pelo depósito extracelular de uma substância amiloide composta por agregados de proteínas mal acopladas que se depositam longe do sítio de síntese, causando disfunção do órgão-alvo e doença clínica. A forma sistêmica mais comum é a amiloidose A (AA) secundária às infecções e às inflamações crônicas, sendo a artrite reumatoide (AR) a causa mais frequente. O tratamento da amiloidose AA consiste no controle ou na resolução da doença de base. O objetivo do presente estudo é relatar um caso de amiloidose renal secundária em paciente com AR refratária de longa duração que apresentou melhora clínica sustentada após o uso de anti-TNFα (etanercepte).

Amyloidosis is a heterogeneous group of diseases characterized by extracellular deposits of a material composed of aggregates of amyloid - a poorly coupled protein - far from the site of synthesis, causing target organ dysfunction and clinical disease. Systemic amyloidosis A (AA), secondary to infections and chronic inflammation, especially rheumatoid arthritis (RA), is the most common form of amyloid deposition. Treatment of AA consists in the control or resolution of the baseline condition. The objective of the present study was to report a case of secondary renal amyloidosis in a patient with long-term refractory RA who presented sustained clinical improvement after the use of anti-TNFα (etanercept).

Clinical features and survival analysis of light-chain amyloidosis associated renal disease / 中国医师进修杂志

Objective To analyze the clinical pathology features of light-chain amyloidosis associated renal disease,and investigate the survival influential factors. Method From January 1998 to March 2009,25 patients with light-chain amyloidosis associated renal disease were reviewed and followed up.Results Of the 25 patients with light-chain amyloidosis associated renal disease,median age was 57(37-69) years old and lamda light-chain predominated (88% ,22/25). Heavy proteinuria and nephrotic syndrome with peripheral edema were typical clinical presentations. Renal biopsy showed that amyloid deposition of light-chain amyloidosis associated renal disease involved the glomeruh mostly, with mesangial area widening. Median survival of all patients was 24.4 months after diagnosis. The estimated 1,2,3 year survival rate was (65 ± 10 )%, (46 ± 12 )% and (15 ± 12 )% respectively. There was significant difference in median survival between the two groups (24.7 months in the group of 14 patients with isolated kidney affected,16.4 months in the group of 11 patients with kidney and other organs involved,P = 0.03). By univariate analysis, kidney associated with other organs amyloidosis and renal dysfunction were relevant to prognosis (P ＜ 0.05) and heart involvement was probably relevant (P = 0.06),whereas sex,age,plasma cell ratio,serum albumin level and hemoglobin level had no relation(P＞ 0.05 ). Multivariate analysis revealed that renal dysfunction at the time of diagnosis was a significant and independent prognostic factor for survival (P ＜0.05). Conclusions Renal dysfunction at the time of diagnosis is the best predictor of survival. The presence of amyloidosis in organs other than the kidney, such as advanced cardiac amyloidosis, predicts a poor survival.

A case of secondary renal amyloidosis complicating Crohn's disease / 대한내과학회지

Secondary amyloidosis is characterized by accumulation of an amorphous proteineous material in the various tissue and orgrans with infectious or inflammatory disease. Renal amyloidosis in Crohn's disease is a rare condition with proteinuria in the most cases and serious clinical complication due to the unfavorable prognosis. We are reporting a case of secondary renal amyloidosis in a 30-year old man with Crohn's disease presenting with nephrotic syndrome and renal failue.

A Case of Early Developed Secondary Renal Amyloidosis in a Patient with Rheumatoid Arthritis (RA) / 대한신장학회잡지

We experienced a case of secondary renal amyloidosis diagnosed by renal biopsy in a patient who had been diagnosed as RA two years ago. A 62-year old man was admitted to neurology departement because of right hemiplegia. During conservative care at neurology department, he was consulted to us because of aggravated generalized edema and proteinuria. He was diagnosed as rheumatoid arthritis and ulcerative colitis two years ago, and then he had taken prednisolone, methotrexate, mesalazine regularly. At physical examination, there was no abnormal finding except pretibial pitting edema and right hemiplegia. In urinalysis, specific gravity was 1.025, pH was 5.5, protein was 4+ and RBC 0-1/ HPF and WBC 0-1/HPF. Total protein of 24 hour's urine was 5.5 g/day. The blood BUN and creatinine level were 16.4 mg/dL, 0.4 mg/dL and cholesterol level were 154 mg/dL, total protein and albumin were 4.4 g/dL and 1.9 g/dL. Serum RA factor and CRP showed high level as 94.90 IU/mL and 118.00 mg/L. On urine electrophoresis, albuminuria was dominant but M-spike was not founded. On urinalysis taken at the time of first diagnosis of rheumatoid arthritis two years ago, proteinuria was negative and serum albumin levels was 3.6 g/dL. At that time, there was no evidence of nephropathy. In renal biopsy, electron microscope showed heavy nonbranching amyloid fibrils accumulated in mesangium and polarized light microscopy after Congo-red staining revealed apple-green birefringent amyloid deposits in glomeruli and blood. So we diagnosed renal amyloidosis associated with RA.

A Case of Secondary Renal Amyloidosis in Children with Juvenile Rheumatoid Arthritis

Amyloidosis comprises a diverse group of systemic and local diseases characterized by organ involvement by the extracellular deposition of fibrils composed of subunits of a variety of normal serum proteins. Secondary amyloidosis is caused by the deposition of amyloid A(AA) protein in chronic inflammatory disease. Juvenile rheumatoid arthritis(JRA) has been known to be the most common cause of secondary amyloidosis. We experienced one case of secondary renal amyloidosis in a 12-year-old girl who had suffered from JRA for several years who had visited our renal clinic to evaluate the proteinuria with microscopic hematuria which was detected by chance at school urine screening examination. Apple green birefringence was observed under polarized light with Congo red stain and characteristic electron microscopic findings was also noted in renal tissues which was obtained by percutaneous renal biopsy. In our knowledge, this is the first case report of secondary renal amyloidosis developed in pediatric age in Korea.

Successful Treatment of Secondary Renal Amyloidosis With Sairei-to in Rheumatoid Arthritis / 日本東洋医学雑誌

The authors report a case of secondary renal amyloidosis associated with rheumatoid arthritis, which responded well to Kampo therapy. A 68-year-old woman was diagnosed as having rheumatoid arthritis in April 1992. Her disease activity was not controlled well with any anti-rheumatic drugs. In September 1996, proteinuria and hematuria were found, and a renal biopsy showed secondary amyloidosis. Proteinuria and hematuria were progressive. The patient was treated with Sairei-to, and by April 1998, proteinuria and hematuria nearly disappeared. This clinical course suggests that Sairei-to is an effective treatment for secondary renal amyloidosis.

Structural-Functional Relationships in Renal Amyloidosis

The pathogenetic mechanism of renal dysfunction in renal amyloidosis is poorly understood. To evaluate the morphologic parameters which are correlated with renal function in this disorder, we have examined renal biopsies from 14 patients with renal amyloidosis by morphometry. Of the 14 patients, 8 were male and 6 were female. They were between 41 and 70 years of age. The serum concentration of albumin and creatinine were 2.1+/-0.7 mg/dl and 1.1+/-0.5 mg/dl, respectively. The 24-hour excretion of urinary protein was 7.9+/-5.2 g. Creatinine clearance was 62+/-23 ml/min/1.73m2. The mean glomerular volume (MGV) was (2.2+/-1.3) 10(6) micrometer3. The surface density of peripheral glomerular basement membrane [Sv (PGBM/glom)] was 0.049+/-0.027 (micrometer3/micrometer3). Volume density of mesangium [Vv (mes/glom)] was 0.31+/-0.14 (micrometer3/micrometer3) and volume density of glomerular amyloid deposition [Vv (amyl/glom)] was 0.21+/-0.14 (micrometer3/micrometer3). The volume density of cortical interstitium [Vv (int/cortex)] was 0.14+/-0.09 (micrometer3/micrometer3). The serum creatinine concentration was significantly correlated with Vv (int/cortex) (r=+0.66, p<0.05). MGV was correlated with Vv (mes/glom) (r=+0.75, p<0.01) and Vv (amyl/glom) (r= +0.68, p<0.05) but showed negative correlation with Sv (PGBM/glom) (r=-0.79, p<0.01). Sv (PGBM/glom) showed negative correlation with Vv (mes/glom) (r=-0.77, p<0.01) and with Vv (amyl/glom) (r=-0.87, p<0.01). Positive correlation was observed between Vv (mes/glom) and Vv (amyl/glom) (r=+0.95, p<0.01). These results suggest that the decreased renal function in patients with amyloidosis is related to interstitial fibrosis rather than glomerular lesions. In addition, glomerular hypertrophy in these patients is related to amyloid deposition in the mesangium and peripheral glomerular basement membrane.

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.