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Myeloma-Related Kidney Disease

(Myeloma Kidney; Myeloma Cast Nephropathy)

By

Frank O'Brien

, MD, Washington University in St. Louis

Last full review/revision Jun 2020| Content last modified Jun 2020
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Patients with multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones causing... read more 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. Glomerular damage is usually the predominant mechanism. The mechanisms by which light chains damage nephrons directly are unknown. Hypercalcemia contributes to renal insufficiency by decreasing renal blood flow.

Tubulointerstitial disease

Types of tubulointerstitial renal disorders in multiple myeloma include

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:

  • Low urine flow

  • Radiocontrast agents

  • Hyperuricemia

  • Nonsteroidal anti-inflammatory drugs (NSAIDs)

  • Elevation of luminal sodium chloride concentration (eg, due to a loop diuretic)

  • Increased intratubular calcium due to the hypercalcemia that often occurs secondary to bone lysis in multiple myeloma

Glomerulopathies

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. Light chain deposition disease, 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 light chain deposition disease with progression to membranoproliferative glomerulonephritis Membranoproliferative Glomerulonephritis Membranoproliferative glomerulonephritis is a heterogeneous group of disorders that share mixed nephritic and nephrotic features and microscopic findings. They mostly affect children. Cause... read more Membranoproliferative Glomerulonephritis and nodular glomerulopathy reminiscent of diabetic nephropathy Diabetic Nephropathy Diabetic nephropathy is glomerular sclerosis and fibrosis caused by the metabolic and hemodynamic changes of diabetes mellitus. It manifests as slowly progressive albuminuria with worsening... read more Diabetic Nephropathy ; nephrotic-range proteinuria is common.

Symptoms and Signs of Myeloma-Related Kidney Disease

Symptoms and signs are predominantly those of the myeloma (eg, skeletal pain, pathologic fractures, diffuse osteoporosis, bacterial infections, hypercalcemia, normochromic-normocytic anemia out of proportion to the degree of renal failure).

Diagnosis of Myeloma-Related Kidney Disease

  • Urine sulfosalicylic acid test or urine protein electrophoresis (myeloma kidney)

  • Biopsy (glomerulopathy)

Diagnosis of myeloma-related kidney disease is suggested by the following combination of findings:

  • Renal insufficiency

  • Bland urine sediment

  • Negative or trace-positive dipstick for protein (unless urine albumin is elevated in a patient with an accompanying nephrotic syndrome)

  • Elevated total urinary protein

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 hours (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 Renal biopsy Biopsy of the urinary tract requires a trained specialist (nephrologist, urologist, or interventional radiologist). Indications for diagnostic biopsy include unexplained nephritic or nephrotic... read more may demonstrate light chain deposition in 30 to 50% of patients with myeloma despite the absence of detectable serum or urine paraproteins by immunoelectrophoresis.

Prognosis for Myeloma-Related Kidney Disease

Kidney disease is a major predictor of overall prognosis in multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones causing... read more Multiple Myeloma . Prognosis is good for patients with tubulointerstitial and glomerular light chain deposition disease 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.

Treatment of Myeloma-Related Kidney Disease

  • Management of multiple myeloma

  • Prevention of volume depletion and maintenance of a high urine flow rate

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.

Key Points

  • Patients with multiple myeloma can sustain tubulointerstitial and glomerular damage by various mechanisms.

  • Suspect myeloma-related kidney disease if patients have unexplained renal insufficiency, bland urinary sediment, and/or increased nonalbumin urinary proteins.

  • Treat myeloma and maintain euvolemia.

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