Browse the corpus

Kidney Manifestations of Deposition Diseases Deposition disease i y Vv i 4 Ig AA amyloid Mixed Fibrillary Immunotactoid cryoglobulinemia glomerulopathy glomerulopathy LS J i a Organized deposits Y Y Monoclonal Myeloma Cast nephropathy gammopathy of renal significance y Y Proliferative Ig-Mediated glomerulonephritis complement activation with monoclonal (C3 GN) Ig deposits } 4 \ Light chain AL amyloid Type | Ig-Associated Ig-Associated deposition cryoglobulinemia fibrillary immunotactoid disease glomerulopathy glomerulopathy . = J Organized deposits

} 4 \ Light chain AL amyloid Type | Ig-Associated Ig-Associated deposition cryoglobulinemia fibrillary immunotactoid disease glomerulopathy glomerulopathy . = J Organized deposits FIGURE 16. Deposition diseases can be divided into five major categories: immunoglobulin (Ig)-related disease, AA amyloid, mixed cryoglobulinemia, fibrillary glomerulopathy, and immunotactoid glomerulopathy. Ig-related disease can be further divided into multiple myeloma and monoclonal gammopathy of renal significance (MGRS). Although some histopathological findings occur more commonly in either multiple myeloma (such as cast nephropathy) or MGRS, most have been reported in either disorder. C3 CN = C3 glomerulopathy (dense deposit disease and C3 glomerulonephritis).

FIGURE 16. Deposition diseases can be divided into five major categories: immunoglobulin (Ig)-related disease, AA amyloid, mixed cryoglobulinemia, fibrillary glomerulopathy, and immunotactoid glomerulopathy. Ig-related disease can be further divided into multiple myeloma and monoclonal gammopathy of renal significance (MGRS). Although some histopathological findings occur more commonly in either multiple myeloma (such as cast nephropathy) or MGRS, most have been reported in either disorder. C3 CN = C3 glomerulopathy (dense deposit disease and C3 glomerulonephritis). tubules (Figure 16). Monoclonal Ig deposits may be caused chronic lymphocytic leukemia can be associated with nephro- by amyloidosis, myeloma, Waldenstrém macroglobulinemia, toxicity. Except for myeloma cast nephropathy seen exclusively or chronic lymphocytic leukemia, or by the clonal expansion with myeloma, all the pathological renal lesions can occur in of Ig-secreting cells that do not meet the strict definition of each of these disorders. Because filtered light chains are endo- these disorders but may cause kidney disease, which has been cytosed by proximal tubule cells and are nephrotoxic, patients termed monoclonal gammopathy of renal significance may present with proximal tubular dysfunction (Fanconi syn- (MGRS). drome); common features include glycosuria, phosphaturia, The pathological findings associated with monoclonal Ig and normal anion gap metabolic acidosis. Creatinine clearance deposition can include proliferative glomerulonephritis, AL may be normal or abnormal. Renal disorders associated with amyloid, type 1 cryoglobulinemia, and, occasionally, fibrillary Ig secretion can be divided into those with organized deposits, and immunotactoid glomerulopathy. Polyclonal Ig deposits such as amyloid, type 1 cryoglobulinemia, fibrillary and include mixed cryoglobulinemia, whereas non-Ig proteins immunotactoid glomerulopathy or those in which the depos- contribute to AA amyloid and to most cases of immunotactoid its are unstructured, such as monoclonal deposition disease and fibrillary glomerulopathy. and proliferative glomerulonephritis with monoclonal Ig deposits (PGNMID).

tubules (Figure 16). Monoclonal Ig deposits may be caused chronic lymphocytic leukemia can be associated with nephro- by amyloidosis, myeloma, Waldenstrém macroglobulinemia, toxicity. Except for myeloma cast nephropathy seen exclusively or chronic lymphocytic leukemia, or by the clonal expansion with myeloma, all the pathological renal lesions can occur in of Ig-secreting cells that do not meet the strict definition of each of these disorders. Because filtered light chains are endo- these disorders but may cause kidney disease, which has been cytosed by proximal tubule cells and are nephrotoxic, patients termed monoclonal gammopathy of renal significance may present with proximal tubular dysfunction (Fanconi syn- (MGRS). drome); common features include glycosuria, phosphaturia, The pathological findings associated with monoclonal Ig and normal anion gap metabolic acidosis. Creatinine clearance deposition can include proliferative glomerulonephritis, AL may be normal or abnormal. Renal disorders associated with amyloid, type 1 cryoglobulinemia, and, occasionally, fibrillary Ig secretion can be divided into those with organized deposits, and immunotactoid glomerulopathy. Polyclonal Ig deposits such as amyloid, type 1 cryoglobulinemia, fibrillary and include mixed cryoglobulinemia, whereas non-Ig proteins immunotactoid glomerulopathy or those in which the depos- contribute to AA amyloid and to most cases of immunotactoid its are unstructured, such as monoclonal deposition disease and fibrillary glomerulopathy. and proliferative glomerulonephritis with monoclonal Ig deposits (PGNMID). Monoclonal Immunoglobulin- Associated Kidney Disease Myeloma Cast Nephropathy A wide array of renal lesions can be caused by clonal expan- Myeloma cast nephropathy occurs in the presence of a sion of Ig-secreting cells, including frank plasma cell neo- markedly increased concentration of free light chains and is plasms. However, paraproteinemia caused by clonal expansion always associated with multiple myeloma. Light chains are of Ig-secreting cells that do not meet the strict definition of freely filtered by the glomerulus and combine with secreted amyloidosis, myeloma, Waldenstré6m macroglobulinemia, or Tamm-Horsfall protein, the main protein in urine, to form

Monoclonal Immunoglobulin- Associated Kidney Disease Myeloma Cast Nephropathy A wide array of renal lesions can be caused by clonal expan- Myeloma cast nephropathy occurs in the presence of a sion of Ig-secreting cells, including frank plasma cell neo- markedly increased concentration of free light chains and is plasms. However, paraproteinemia caused by clonal expansion always associated with multiple myeloma. Light chains are of Ig-secreting cells that do not meet the strict definition of freely filtered by the glomerulus and combine with secreted amyloidosis, myeloma, Waldenstré6m macroglobulinemia, or Tamm-Horsfall protein, the main protein in urine, to form 56

obstructing casts. Patients with cast nephropathy present Amyloidosis with acute or slowly progressive kidney injury. Serum free Amyloidosis is a disorder characterized by kidney and other light chains are extremely elevated (usually >50 mg/dL organ injury caused by the deposition of insoluble amyloid [500 mg/L]). Treatment is aimed at reducing the production proteins that form B-pleated sheets. Although amyloid can be and concentration of free light chains using chemotherapy. made up of numerous proteins, kidney disease is most com- Nephrotoxins, such as contrast media or NSAIDs, and monly caused by AL amyloid or AA amyloid. AL amyloid is volume depletion should be avoided in these patients. The composed of monoclonal A (most commonly) or « light chains benefit of plasmapheresis to reduce light chains and produced by either MGRS or myeloma; AA amyloid is formed improve kidney function is undetermined, but some by serum amyloid A protein, an acute phase reactant produced experts use plasmapheresis as an adjunctive treatment to in various inflammatory diseases such as rheumatoid arthritis, chemotherapy. inflammatory bowel disease, chronic osteomyelitis, and famil- ial Mediterranean fever. Patients with renal amyloid frequently

obstructing casts. Patients with cast nephropathy present Amyloidosis with acute or slowly progressive kidney injury. Serum free Amyloidosis is a disorder characterized by kidney and other light chains are extremely elevated (usually >50 mg/dL organ injury caused by the deposition of insoluble amyloid [500 mg/L]). Treatment is aimed at reducing the production proteins that form B-pleated sheets. Although amyloid can be and concentration of free light chains using chemotherapy. made up of numerous proteins, kidney disease is most com- Nephrotoxins, such as contrast media or NSAIDs, and monly caused by AL amyloid or AA amyloid. AL amyloid is volume depletion should be avoided in these patients. The composed of monoclonal A (most commonly) or « light chains benefit of plasmapheresis to reduce light chains and produced by either MGRS or myeloma; AA amyloid is formed improve kidney function is undetermined, but some by serum amyloid A protein, an acute phase reactant produced experts use plasmapheresis as an adjunctive treatment to in various inflammatory diseases such as rheumatoid arthritis, chemotherapy. inflammatory bowel disease, chronic osteomyelitis, and famil- ial Mediterranean fever. Patients with renal amyloid frequently Monoclonal Gammopathy present with nephrotic-range proteinuria. Less commonly, amyloid can affect only the renal vasculature or tubular inter- of Renal Significance stitium and have minimal or no proteinuria. Treatment is Monoclonal gammopathy of renal significance (MGRS) is char- aimed at the underlying disease. See MKSAP 19 Hematology acterized by kidney damage caused by monoclonal Ig that is for more information on amyloidosis. secreted by a B cell or plasma cell clone not meeting diagnostic criteria for multiple myeloma or a lymphoproliferative disor- der. In the absence of the otherwise unexplained kidney Cryoglobulinemia injury, these patients would be thought to have monoclonal Although all three types of cryoglobulinemia can cause kid- gammopathy of unknown significance. All pathological find- ney disease, kidney involvement occurs most frequently with ings associated with the clonal expansion of Ig-secreting cells type II (mixed Ig) cryoglobulinemia and is usually associated can be seen in both myeloma and MGRS. The underlying with hepatitis C virus infection and small-vessel vasculitis. pathology is likely determined by the characteristics of the Patients can present with a nephritic picture: elevated secreted protein. Entities associated with MGRS include serum creatinine, hypertension, proteinuria, and hematuria. PGNMID, C3 glomerulopathy with monoclonal gammopathy, Membranoproliferative glomerulonephritis is usually noted AL amyloid, type 1 cryoglobulinemia, fibrillary glomerulopa- on biopsy. Occasionally, a rapidly progressive glomerulone- thy, and immunotactoid glomerulopathy. phritis with crescent formation can occur. A palpable purpu- Kidney manifestations of MGRS are usually caused by ric rash is frequently present on the lower extremities. deposition of monoclonal Ig light chains. Patients can present Treatment is aimed at eradication of the hepatitis C virus. See with nephrotic or subnephrotic proteinuria, hematuria, and MKSAP 19 Rheumatology for a discussion of cryoglobuline- elevated serum creatinine. mic vasculitis. See MKSAP 19 Hematology for a discussion of Kidney biopsy is necessary to make the diagnosis. Further all three types of cryoglobulinemia. testing may include serum and urine protein electrophoresis with immunofixation, measurement of free light chains, and bone marrow biopsy. Treatment is aimed at eradication of the Fibrillary and Immunotactoid expanded clonal line. Glomerulopathy Although rare, both fibrillary and immunotactoid glomer- ulopathy are increasingly recognized causes of kidney dis- Monoclonal Immunoglobulin ease. These diseases are caused by glomerular deposition of

Monoclonal Gammopathy present with nephrotic-range proteinuria. Less commonly, amyloid can affect only the renal vasculature or tubular inter- of Renal Significance stitium and have minimal or no proteinuria. Treatment is Monoclonal gammopathy of renal significance (MGRS) is char- aimed at the underlying disease. See MKSAP 19 Hematology acterized by kidney damage caused by monoclonal Ig that is for more information on amyloidosis. secreted by a B cell or plasma cell clone not meeting diagnostic criteria for multiple myeloma or a lymphoproliferative disor- der. In the absence of the otherwise unexplained kidney Cryoglobulinemia injury, these patients would be thought to have monoclonal Although all three types of cryoglobulinemia can cause kid- gammopathy of unknown significance. All pathological find- ney disease, kidney involvement occurs most frequently with ings associated with the clonal expansion of Ig-secreting cells type II (mixed Ig) cryoglobulinemia and is usually associated can be seen in both myeloma and MGRS. The underlying with hepatitis C virus infection and small-vessel vasculitis. pathology is likely determined by the characteristics of the Patients can present with a nephritic picture: elevated secreted protein. Entities associated with MGRS include serum creatinine, hypertension, proteinuria, and hematuria. PGNMID, C3 glomerulopathy with monoclonal gammopathy, Membranoproliferative glomerulonephritis is usually noted AL amyloid, type 1 cryoglobulinemia, fibrillary glomerulopa- on biopsy. Occasionally, a rapidly progressive glomerulone- thy, and immunotactoid glomerulopathy. phritis with crescent formation can occur. A palpable purpu- Kidney manifestations of MGRS are usually caused by ric rash is frequently present on the lower extremities. deposition of monoclonal Ig light chains. Patients can present Treatment is aimed at eradication of the hepatitis C virus. See with nephrotic or subnephrotic proteinuria, hematuria, and MKSAP 19 Rheumatology for a discussion of cryoglobuline- elevated serum creatinine. mic vasculitis. See MKSAP 19 Hematology for a discussion of Kidney biopsy is necessary to make the diagnosis. Further all three types of cryoglobulinemia. testing may include serum and urine protein electrophoresis with immunofixation, measurement of free light chains, and bone marrow biopsy. Treatment is aimed at eradication of the Fibrillary and Immunotactoid expanded clonal line. Glomerulopathy Although rare, both fibrillary and immunotactoid glomer- ulopathy are increasingly recognized causes of kidney dis- Monoclonal Immunoglobulin ease. These diseases are caused by glomerular deposition of Deposition Disease organized fibrillar or tubular structures that are larger than amyloid and do not stain with Congo red. Proteinuria, fre- Monoclonal light chains (usually «) or heavy chains can be quently in the nephrotic range, and hematuria are com- deposited in the kidney and manifest as proteinuria and kid- mon. Although the pathogenesis of these entities is ney failure. Unlike AL amyloid, these proteins do not form unknown, both have been associated with paraproteine- B-pleated sheets and do not stain with Congo red. These mia. Treatment is usually unsuccessful, and kidney out- deposits can be limited to the basement membrane, giving a comes are poor. microscopic appearance similar to that of diabetic nodular sclerosis (light chain deposition disease) or can activate com- plement and induce a proliferative glomerulonephritis e Patients with myeloma cast nephropathy present with (PGNMID). In some cases, an underlying plasma cell dyscrasia acute or slowly progressive kidney injury and have or lymphoproliferative disorder can be identified, but criteria extremely elevated serum free light chains. for myeloma or chronic lymphocytic leukemia are often (Continued) absent.

Deposition Disease organized fibrillar or tubular structures that are larger than amyloid and do not stain with Congo red. Proteinuria, fre- Monoclonal light chains (usually «) or heavy chains can be quently in the nephrotic range, and hematuria are com- deposited in the kidney and manifest as proteinuria and kid- mon. Although the pathogenesis of these entities is ney failure. Unlike AL amyloid, these proteins do not form unknown, both have been associated with paraproteine- B-pleated sheets and do not stain with Congo red. These mia. Treatment is usually unsuccessful, and kidney out- deposits can be limited to the basement membrane, giving a comes are poor. microscopic appearance similar to that of diabetic nodular sclerosis (light chain deposition disease) or can activate com- plement and induce a proliferative glomerulonephritis e Patients with myeloma cast nephropathy present with (PGNMID). In some cases, an underlying plasma cell dyscrasia acute or slowly progressive kidney injury and have or lymphoproliferative disorder can be identified, but criteria extremely elevated serum free light chains. for myeloma or chronic lymphocytic leukemia are often (Continued) absent. 57