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Myeloma-Related Kidney Disease
(Myeloma Kidney; Myeloma Cast Nephropathy)
Patients with multiple myeloma overproduce monoclonal Ig light chains (Bence Jones proteins); these light chains are filtered by glomeruli, are nephrotoxic, and, in their various forms (free, tubular casts, amyloid), can damage virtually all areas of the kidney parenchyma. Diagnosis is by urine tests (sulfosalicylic acid test or protein electrophoresis) or renal biopsy. Treatment focuses on the multiple myeloma and ensuring adequate urine flow. Myeloma-related kidney disease is rarely caused by Ig heavy chains.
Tubulointerstitial disease and glomerular damage are the most common types of renal damage. The mechanisms by which light chains damage nephrons directly are unknown. Hypercalcemia contributes to renal insufficiency by decreasing renal blood flow.
Types of tubulointerstitial renal disorders in multiple myeloma include
Myeloma kidney (myeloma cast nephropathy)
Acquired Fanconi syndrome (proximal tubular disease)
Interstitial light chain deposition, causing acute tubular necrosis
Light chains saturate the reabsorptive capacity of the proximal tubule, reach the distal nephron, and combine with filtered proteins and Tamm-Horsfall mucoprotein (secreted by cells of the thick ascending limb of Henle) to form obstructive casts. The term myeloma kidney or myeloma cast nephropathy generally refers to renal insufficiency caused by the tubulointerstitial damage that results. Factors that predispose to cast formation include the following:
Other types of tubulointerstitial lesions that occur with Bence Jones proteinuria include proximal tubular transport dysfunction, causing Fanconi syndrome, and light chain interstitial deposition with inflammatory infiltrates and active tubular damage, which can cause acute tubular necrosis.
Types of glomerular renal disorders in multiple myeloma include
AL amyloidosis results in glomerular deposition of AL amyloid in the mesangial, subepithelial, or subendothelial areas or a combination. Amyloid deposition is with randomly oriented, nonbranching fibrils composed of the variable regions of lambda light chains. LCDD, which also can occur with lymphoma and macroglobulinemia, is glomerular deposition of nonpolymerized light chains (ie, without fibrils), generally the constant regions of kappa chains.
Rarely, a nonproliferative, noninflammatory glomerulopathy that causes nephrotic-range proteinuria can develop in advanced myeloma-related renal disease. A proliferative glomerulonephritis occasionally develops as an early form of LCDD with progression to membranoproliferative glomerulonephritis and nodular glomerulopathy reminiscent of diabetic nephropathy; nephrotic-range proteinuria is common.
Diagnosis of myeloma-related kidney disease is suggested by the following combination of findings:
The diagnosis should be suspected even in patients without a history of or findings suggesting multiple myeloma, particularly if total urinary protein is elevated out of proportion to urinary albumin). Total urinary protein is measured over 24 h (and is often elevated enough to suggest nephrotic syndrome) or as a spot measurement (eg, using the urine sulfosalicylic acid test); urinary albumin is measured by dipstick.
Diagnosis of light chain tubulointerstitial disease (myeloma kidney) is confirmed by a markedly positive urine sulfosalicylic acid test suggesting significant nonalbumin proteins, by urine protein electrophoresis (UPEP), or both.
Diagnosis of glomerulopathy is confirmed by renal biopsy. Renal biopsy may demonstrate light chain deposition in 30 to 50% of patients with myeloma despite the absence of detectable serum or urine paraproteins by immunoelectrophoresis.
Kidney disease is a major predictor of overall prognosis in multiple myeloma. Prognosis is good for patients with tubulointerstitial and glomerular LCDD who receive treatment. Prognosis is worse for patients with AL amyloidosis, in whom amyloid deposition continues and progresses to renal failure in most cases. In either form without treatment, virtually all renal lesions progress to renal failure.
Management of multiple myeloma and prevention of volume depletion (eg, using normal saline for volume expansion) to maintain a high urine flow rate are the primary treatments. In addition, factors that worsen renal function (eg, hypercalcemia, hyperuricemia, use of nephrotoxic drugs) should be avoided or treated.
Several measures are often recommended but are of unproved efficacy. Plasma exchange may be tried to remove light chains. Alkalinization of the urine to help change the net charge of the light chain and reduce charge interaction with Tamm-Horsfall mucoprotein may make the light chains more soluble. Colchicine may be given to decrease secretion of Tamm-Horsfall mucoprotein into the lumen and to decrease the interaction with light chains, thus decreasing toxicity. Loop diuretics may be avoided to prevent volume depletion and high distal sodium concentrations that can worsen myeloma-related kidney disease.
Patients with multiple myeloma can sustain tubulointerstitial or glomerular damage by various mechanisms.
Suspect myeloma-related kidney disease if patients have unexplained renal insufficiency, bland urinary sediment, and/or increased non-albumin urinary proteins.
Treat myeloma and maintain euvolemia.
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