
(See also Overview of Tubulointerstitial Diseases Overview of Tubulointerstitial Diseases Tubulointerstitial diseases are clinically heterogeneous disorders that share similar features of tubular and interstitial injury. In severe and prolonged cases, the entire kidney may become... read more .)
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
Myeloma kidney (myeloma cast nephropathy)
Interstitial light chain deposition, causing acute tubular necrosis Acute Tubular Necrosis (ATN) Acute tubular necrosis (ATN) is kidney injury characterized by acute tubular cell injury and dysfunction. Common causes are hypotension or sepsis that causes renal hypoperfusion and nephrotoxic... read more
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
Other types of tubulointerstitial lesions that occur with Bence Jones proteinuria include proximal tubular transport dysfunction, causing Fanconi syndrome, Fanconi Syndrome Fanconi syndrome consists of multiple defects in renal proximal tubular reabsorption, causing glucosuria, phosphaturia, generalized aminoaciduria, and bicarbonate wasting. It may be hereditary... read more and light chain interstitial deposition with inflammatory infiltrates and active tubular damage, which can cause acute tubular necrosis Acute Tubular Necrosis (ATN) Acute tubular necrosis (ATN) is kidney injury characterized by acute tubular cell injury and dysfunction. Common causes are hypotension or sepsis that causes renal hypoperfusion and nephrotoxic... read more .
Glomerulopathies
Types of glomerular renal disorders in multiple myeloma include
Light chain deposition disease
Heavy chain deposition, rarely
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 (MPGN) is characterized by a pattern of glomerular injury on light microscopy, including hypercellularity and thickening of the glomerular basement membrane... read more 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
; nephrotic-range proteinuria is common.
Symptoms and Signs
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
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
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 that cause... read more . 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
Management of multiple myeloma
Prevention of volume depletion and maintenance of a high urine flow rate
Management of multiple myeloma Treatment 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 that cause... read more and prevention of volume depletion Volume Depletion Volume depletion, or extracellular fluid (ECF) volume contraction, occurs as a result of loss of total body sodium. Causes include vomiting, excessive sweating, diarrhea, burns, diuretic use... read more (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.
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.
Drugs Mentioned In This Article
Drug Name | Select Trade |
---|---|
sodium chloride |
4-Way Saline, Adsorbonac, Altamist, Ayr Allergy & Sinus, Ayr Baby Saline, Ayr Saline Nasal, BD Posiflush Normal Saline, BD Posiflush Sterile Field Normal Saline, BD Posiflush SureScrub Normal Saline, Blairex Broncho Saline, Breathe Free Saline, Deep Sea , Entsol, HyperSal, Hyper-Sal, Hypertears, Little Remedies for Noses, Little Remedies Stuffy Nose, Monoject Sodium Chloride, Muro 128, NebuSal , Ocean, Ocean Complete, Ocean For Kids, Pediamist, PULMOSAL, Rhinaris, Rhinaris Lubricating, Saljet , Saljet Rinse, SaltAire, Sea Soft, Trichotine, Wound Wash, XYNASE, ZARBEE'S Soothing Saline Nasal Mist |
albumin |
Albuked , Albumarc, Albuminar, Albuminex, AlbuRx , Albutein, Buminate, Flexbumin, Kedbumin, Macrotec, Plasbumin, Plasbumin-20 |
colchicine |
ColciGel, Colcrys , GLOPERBA, LODOCO, MITIGARE |