Light chain associated cast nephropathy and renal alamyloidosis. The pathologist viewing the biopsy can tell it is light chain deposition disease because it has a different appearance from other deposition diseases. Lcs are normally cleared by the kidneys, but in lcdd, these light chain deposits damage organs and cause disease. Background small deposits of amyloid are often found in the hearts of elderly patients. The spectrum of renal complications associated with paraproteins is heterogeneous, with two major categories corresponding to the. Courtesy of madeleine moussa, md, frcpc, department of pathology. Light chain associated cast nephropathy and renal alamyloidosis represent two further pathologies going along with monoclonal gammopathy of renal significance and multiple myeloma.
Light microscopy hematoxylin and eosin stain at 25x power showing nodular glomerulosclerosis arrow and thickening of the basement membrane. Light chain cast nephropathy and acute renal failure. The biology of immunoglobulin free light chains and kidney injury. The spectrum of renal complications associated with paraproteins is heterogeneous, with two major categories. Renal diseases associated with multiple myeloma and. Pdf structural analysis of urinary light chains and. Cutaneous haemorrhage induced by minimal trauma as a sign of light chain. Renal tubular dysfunction associated with lightchain proteinuria. Ig light chainassociated amyloidosis is a fatal plasma cell proliferative disorder that is characterized by fibril deposition in various organs. This study was undertaken to investigate factors that influence renal response.
The characterization of these early events, which are similar to those encountered in congenital lysosomal disorders, provides a basis for the reported differential lc toxicity and new perspectives on lc. Light chain deposition disease, like al amyloidosis, is a systemic disease caused by the overproduction and extracellular deposition of a monoclonal immunoglobulin light chain chapter 193. Bencejones cast nephropathy and light chain deposit disease, although before the renal biopsy there was no documentation of an abnormal urine or serum light or heavy chain. The clinical features of ssa that involve the heart are ill. Mg are frequently associated with renal disease, and up to 50% of patients with mm already. Matthew beekley, phd, assistant professor in the department of kinesiology at the university of indianapolis, answers common questions regarding the management of nutrition and chronic kidney disease. Acute renal failure developed in a patient with a normal serum creatinine level, after treatment with rifampin was begun for tuberculosis. Amyloidosis al is a common cause of nephrotic syndrome in nondiabetic, nonhypertensive adults. Light chain cast nephropathy and acute renal failure associated with rifampin therapy. Light chain deposition stimulates mesangial and matrix expansion leading to.
The three types of human lightchainassociated diseasemyeloma kidney disease myeloma cast nephropathy, lightchain deposition disease, and al amyloidosisare characterized by renal and systemic deposition of monoclonal light chains, i. Chronic kidney disease symptoms and causes mayo clinic. Serum free light chain levels and renal function at diagnosis in. We find this sentence difficult to accept, since lightchainassociated plasmacell dyscrasia is known to be related to renal disorders. The finding of a monoclonal protein, particularly of lambda type, should lead to a subcutaneous fat aspirate or bone marrow biopsy to. However, the patient did not regain renal function even when less than 5% plasma cells were detected in the bone marrow. Multiple myeloma is a malignant plasma cell disorder characterized by the overproduction of monoclonal proteins. Light chainassociated renal disorders differential diagnoses. Senile systemic amyloidosis presenting with heart failure.
The spectrum of renal complications associated with paraproteins is heterogeneous, with two major. The kidneys are almost always affected and this often leads to kidney failure. Severity of baseline proteinuria predicts renal response. Background monoclonal overproduction of kappa andor lambda light chains might result in renal light chain deposition disease.
In chronic kidney disease ckd, light chains are filtered by the glomeruli and then reabsorbed by the proximal tubuli 5. Serum free light chains can also be increased, usually with a normal kappalambda ratio, with some connective tissue disorders, inflammatory conditions, neurological conditions, and some cancers but are not typically monitored in people with these conditions. Screening and differential diagnosis of renal light chain. Renal impairment ri is common in multiple myeloma mm and is associated with poor survival. Update on nutrition and chronic kidney disease medscape. Although paraproteinemic renal diseases are often associated. The presence of lightchain pro teins in the urine is associated with a number of systemic diseases and a variety of renal disorders. Al amyloidosis amyloid light chain cleveland clinic. In other deposition diseases, the chains will appear to form a pattern and are found in one particular section of the kidney. Most often, this is the result of the monoclonal proteins, which can injure the kidney via several mechanisms. Immunoglobulin light chain al amyloidosis previously referred to as primary amyloidosis, light chain deposition disease lcdd, and heavy chain deposition disease hcdd are monoclonal plasma cell proliferative disorders that are characterized by tissue deposits of light chain or heavy chain fragments, leading to organ dysfunction. Transient monoclonal gammopathy induced by disseminated.
Association between free light chain levels, and disease. In some cases, direct invasion by myeloma cells andor bone marrow cells can also result in kidney injury. Light chainassociated renal disorders clinical presentation. The biology of immunoglobulin free light chains and kidney. Structural analysis of urinary light chains and proteomic. This is the first reported case of a transient monoclonal gammopathy igg lambda light chain associated with a staphylococcus aureus infection that was complicated with renal abscess and vertebral spondylodiscitis in a previously healthy 68yearold male. Therefore, nonsecretory myeloma and light chain diseases are difficult to diagnose and monitor during and after treatment with these aforementioned methods. All compartments of the kidney may be affected, from the glomerulus to the tubulointerstitium, in a wide variety of disease patterns. Monoclonal light chain crystalline podocytopathy and. They are associated to different forms of renal disease, like nephropathy due to ig deposition or precipitation. However, extensive deposition of transthyretinderived amyloid fibrils in the heart senile systemic amyloidosis ssa can cause heart failure. Renal insufficiency and failure hematology american. Flcs are present in similar concentrations in the vascular and extravascular compartments 529.
In both registries, the terms multiple myeloma and lightchain associated nephropathy usrds or lightchain deposition disease lcdd eraedta registry prd code 82 are considered together although these terms designate completely different entities. V domain involvement is now demonstrated in all monoclonal light chain lcrelated renal pathologies, but specific peculiarities including lc isotypes, germline v domains, somatic mutations, and cellular. Kidney injury caused by immunoglobulin free light chains flcs in the setting of plasma cell dyscrasias is common and associated with increased morbidity and mortality. Multiple myeloma mm, light or heavychain deposition disease lcdd hcdd, light or heavychainassociated amyloidosis alah, and acquired fanconi syndrome afs represent a group of disorders characterized by the presence of monoclonal plasma cells in bone marrow and their homogeneous immunoglobulin productsi. Ig free light chains lcs may accumulate within epithelial cells, causing proximal tubule pt dysfunction and renal fanconi syndrome. Signs and symptoms of chronic kidney disease develop over time if kidney damage progresses slowly. The clinical differential diagnosis included light chain induced nephropathies. The kidney is 1 of the major target organs of multiple myeloma. Chronic renal failure is classified according to glomerular filtration rate as estimated by the mdrd modification of diet in renal disease formula, while rifle risk, injury, failure, loss and endstage renal disease and akin acute renal injury network criteria may be used for the definition of the severity of acute renal injury. Experimental model of human lightchainassociated disease.
In patients with light chains deposition disease, the. All adult patients with nephrotic syndrome should have immunofixation of serum and urine as a screen. Courtesy of madeleine moussa, md, frcpc, department of pathology, london health sciences centre, london, ontario, canada. Figure 1principal features of monoclonal immunoglobulin light chainrelated renal disorders, with contribution of experimental models red. Impaired lysosomal function underlies monoclonal light chainassociated renal fanconi syndrome alessandro luciani. Of these, approximately 46% were classified as proximal tubulecentered lesions, also referred to as monoclonal light chainassociated proximal tubulopathies. Structural analysis of urinary light chains and proteomic analysis of hyaline tubular casts in light chain associated kidney disorders article pdf available in peerj 76. The value of serum free light chain assay in patients with.
Renal disorders that masquerade as acute glomerulonephritis andor. As a consequence, the vascular compartment may contain only 1520% of the total amount of flcs in the body. To the best of our knowledge, this is the first report of simultaneous light chain proximal tubulopathy, crystalstoring histiocytosis, and myeloma cast nephropathy in. Serum free light chains sflc, kappa and lambda are proteins produce by immune cells that are not part of whole intact antibodies. Monoclonal gammopathies and associated disorders warren brenner m. Lightchainassociated amyloidosis has beentermed alamyloidosis 1, 2. The major diseases in the spectrum of myeloma related kidney disease include cast nephropathy, light chaindepositiondiseaselcdd,andalamyloidosis.
Learn about amyloid light chain amyloidosis from cleveland clinic. Lab tests measure free light chains in the blood and a kappalambda ratio to help diagnose multiple myeloma and related diseases. Glomerular diseases that may be associated with paraproteinemias include amyloid. Proximal tubulopathies associated with monoclonal light. Renal failure due to light chain deposition disease revista nefrologia. An overview of the kidney and monoclonal free light chains.
Light chain deposition disease lcdd is a rare blood cell disease which is characterized by deposition of fragments of infectionfighting immunoglobulins, called light chains lcs, in the body. Renal impairment is a common complication of multiple myeloma. Renal biopsy findings the portion of the biopsy for light microscopy disclosed. Highdose melphalan followed by autologous stem cell transplantation has been shown to improve organ dysfunction and survival. Fs often occurs in the setting of smoldering myeloma and features cytoplasmic crystalline inclusions of monoclonal. Bencejones cast nephropathy and light chain deposit disease. The bence jones protein bjp represents a homogeneous population of immunoglobulin light chains of either kappa type or lambda type and is. Myelomarelated kidney disease advances in chronic kidney. Disorders of plasma and b cells leading to paraproteinemias are associated with a variety of renal diseases. Lc in proximal tubular cells and malignant plasma cells. Mgrsassociated renal lesions comprise a wide variety of kidney disorders caused by monoclonal immunoglobulins and their fragments, including light chains or heavy chains. Light chain diseases urine protein profile myeloma.
These proximal tubulopathies were divided into 4 groups defined by characteristic immunomorpho. Inthesecases, light chains or, more commonly, lightchain fragments but not heavy chains have beenfound to be the principal amyloid protein constituent 1. While cast nephropathy often manifests with acute kidney injury, alamyloidosis is rather accompanied with chronic kidney disease. Main renal disorders related to monoclonal immunoglobulin deposition or. A wide range of renal manifestations and pathologies involving different mechanisms have been described with these disorders. As we have shown in 289 patients with plasmacell dyscrasia, lightchain proteinuria is strongly associated with a worse renal prognosis hazard ratio 218, 95% ci 110432. Impaired lysosomal function underlies monoclonal light chainassociated renal fanconi syndrome. Fanconis syndrome fs is a disorder of sodiumdependent proximal tubule reabsorption, which may complicate plasma cell disorders producing a free monoclonal light chain lc. Impaired lysosomal function underlies monoclonal light. Renal manifestation of multiple myeloma or elevated free light chains due to monoclonal gammopathy frequently manifest in light chain associated kidney disorders with different forms of deposits in renal compartments leung et al.
Understanding the mechanisms of injury and associated nephropathies provides a framework that aids clinicians in prompt diagnosis and appropriate adjunctive treatment of these disorders. This protein misfolding disorder can affect the heart, kidney, skin, stomach, small and large intestines, nerves, and liver causing these organs and tissues to thicken and eventually lose function. Cutaneous haemorrhage induced by minimal trauma as a sign. Usa91 1994 3035 proteins in vitro andin vivo indicates the potential value of analytical sizeexclusion chromatography to differentiate pathologic from nonpathologic human monoclonal light chains andto gain newinsight into the pathogenesis ofthe humanlightchainassociated renal andsystemic diseases.