MONOCLONAL IMMUNOGLOBULINS AND RENAL DISEASE
Monoclonal immunoglobulins are associated with a wide variety of renal manifestations (Table 146-4), of which myeloma-associated cast nephropathy is the most common. The physiochemical characteristics of the monoclonal immunoglobulin, or more commonly the monoclonal light or heavy chains, determine the clinical phenotype in individual pts, most commonly cast nephropathy, light chain deposition disease, and AL amyloidosis. In cast nephropathy, filtered light chains aggregate and cause tubular obstruction, tubular damage, and interstitial inflammation. Pts can present with CKD or with AKI; important predisposing factors in acute cast nephropathy include hypercalcemia and volume depletion.
|Cast nephropathy||Most common cause of CKD in myeloma|
|Tubular obstruction with light chains|
|Acute or chronic renal failure|
|Light chain deposition disease||Nephrotic syndrome, chronic renal failure, ∼40% have associated myeloma|
|Heavy chain deposition disease||Nephrotic syndrome, chronic renal failure|
|Monoclonal immunoglobulin deposition disease||Nephrotic syndrome, chronic renal failure|
|AL amyloidosis||Nephrotic syndrome, cardiac/endocrine/neuropathic involvement|
|∼10% have associated myeloma|
|Renal tubular dysfunction (RTA, nephrogenic DI, etc.)|
|Hyperviscosity syndrome||With Waldenström’s macroglobulinemia|
|Fanconi syndrome||Glucosuria, aminoaciduria, phosphaturia, ± hypouricemia, proximal RTA, etc.|
Diagnosis of cast nephropathy relies on the detection of monoclonal light chains in serum and/or urine, typically by protein electrophoresis and immunofixation. Dipstick analysis of the urine for protein is classically negative in cast nephropathy, despite the excretion of up to several grams a day of light chain protein; light chains are not detected by this screening test, which tests only for albuminuria. In contrast, the glomerular deposition of light chains in light chain deposition disease or AL amyloidosis can result in nephrotic-range proteinuria (Table 146-4), with strongly positive urine dipstick for protein.
Management of cast nephropathy encompasses aggressive hydration, treatment of hypercalcemia if present, and chemotherapy for the associated multiple myeloma. Some experts advocate the use of plasmapheresis for pts with severe AKI, high levels of serum monoclonal light chains, and a renal biopsy demonstrating cast nephropathy.
Filtered light chains and multiple other low-molecular-weight proteins are also endocytosed and metabolized by the proximal tubule. Rarely, specific light chains generate crystalline depositions within proximal tubule cells, causing a Fanconi syndrome; again, this property appears to be caused by the specific physicochemical characteristics of the associated light chains. Fanconi syndrome or dysfunction of the distal nephron (hyperkalemic acidosis or nephrogenic DI) may also complicate renal amyloidosis.
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