Light Chain-Associated Renal Disorders Workup

Updated: Sep 10, 2019
  • Author: Malvinder S Parmar, MBBS, MS, FRCPC, FACP, FASN; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Workup

Laboratory Studies

Urinalysis

Urinalysis results may indicate low-grade proteinuria. A discrepancy between the results of a urine dipstick test for protein and the findings from a test for 24-hour urine protein excretion should suggest the possibility of light-chain proteinuria. Light-chain proteins in the urine cannot be detected using Albustix or other dipstick methods.

Perform the Putnam heat test or the sulfosalicylic acid (SSA) test (with Exton reagent) to help detect urinary light-chain proteins. The results from either test are insensitive. The Putnam heat test can help detect urinary light chains only when the concentration exceeds 150 mg/dL. False-negative results are common with the SSA test if the specific gravity of urine is less than 1.01.

If a patient has a negative result from the Albustix test (which detects albumin) and a positive result from the SSA test, consider the possibility of light-chain proteinuria.

Urine immunoelectrophoresis

Light-chain proteins are best detected and identified using immunoelectrophoresis with monospecific antikappa and antilambda sera.

CBC count

Anemia may be present in patients with multiple myeloma.

Serum electrolytes and serum bicarbonate with anion gap calculation

Because of the cationic charge of paraproteins, the level of this serum chloride is slightly elevated and the anion gap (see the Anion Gap calculator) is lower than normal.

Peripheral smear

Rouleaux formation is observed in patients with multiple myeloma and Waldenström macroglobulinemia.

Serum calcium

Hypercalcemia may be present in patients with multiple myeloma.

Serum protein electrophoresis and immunoelectrophoresis

These can be used to evaluate and quantitate the abnormal monoclonal spike.

Serum free-light chain (FLC, Freelite) assay

Free light chains (FLC, quantitative assay) have been shown to be sensitive and specific for various light chain–associated disorders. In 110 patients with amyloidosis, the FLC kappa/lambda ratio was positive in 91% of patients (compared with 69% of patients) for serum immunofixation (IFE) and in 83% of patients for urine IFE. [10] The combination of serum IFE and serum FLC detected an abnormal result in 99% of patients. Serum free light assay is mainly helpful in monitoring response to therapy. [11] In some patients with negative serum and urine electrophoresis for monoclonal protein, serum free light chain was helpful in establishing diagnosis. [12]

 Most cases of myeloma cast nephropathy occur in patients with serum FLCs above 100 mg/dL, and FLCs less than 70 mg/dL are rarely observed. [13]

Serum electrolytes, including serum bicarbonate

Patients with tubular dysfunction may present with low or normal anion gap metabolic acidosis.

Urine for glucose

Glucosuria may be observed in the absence of hyperglycemia.

Nephrotic-range proteinuria

This may be present in patients with AL amyloidosis.

Serum albumin

Hypoalbuminemia and a reversal of the albumin-globulin ratio may be present.

Erythrocyte sedimentation rate

This is often significantly elevated in patients with myeloma.

Hepatic profile

A moderate degree of liver dysfunction may be observed because of the deposition of light chains in the liver or other organs.

Serum creatinine 

An unusual case of light chain proximal tubulopathy (LCPT) without any usual sign of tubular cell dysfunction apart from mild proteinuria, but with a complete abolishment of tubular secretion of creatinine has been reported. [14]  

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Imaging Studies

Renal ultrasound

Renal ultrasound images can help assess renal echogenicity and renal size in patients presenting with renal failure. Findings can also help to rule out renal calcification or stones. One third of the patients may have enlarged kidneys.

Skeletal survey

Results may show lytic bone lesions, osteoporosis, or compression fracture(s) in patients with possible multiple myeloma.

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Procedures

Findings from bone marrow aspiration and biopsy can be used to assess plasma cell infiltration.

Kidney biopsy is not mandatory, but it is useful when causes of renal failure other than myeloma are under consideration.

When AL amyloidosis is suggested, consider performing a biopsy on the affected tissue. The diagnostic yield of various tissue biopsies is as follows:

  • Kidney or liver biopsy - Greater than 90%

  • Abdominal fat pad biopsy - 85%

  • Rectal biopsy - 50-80%

  • Gingival biopsy - 60%

  • Skin biopsy - 58%

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Histologic Findings

Light chain–induced tubular dysfunction (Fanconi syndrome)

Needlelike crystals may be seen in renal tubular epithelial cells of some patients with light-chain proteinuria and Fanconi syndrome.

Classic myeloma kidney (cast nephropathy)

This condition is characterized by eosinophilic, dense, homogeneous casts that are often fractured or laminated and are partially surrounded by multinucleated foreign body–type giant cells. Congo red–positive casts have been reported in a few cases. Intratubular light chains apparently may undergo alteration in situ, resulting in amyloid formation.

Light-chain deposition disease

The most characteristic histologic lesion of LCDD is nodular glomerulosclerosis (see the first image shown below) that is virtually indistinguishable from diabetic glomerulosclerosis when using light microscopy. Routine immunofluorescence findings are negative because the antibodies used to identify the immunoglobulins are directed at the heavy chains of immunoglobulins. Therefore, as the name suggests, special stains for light chains must be used to identify this (see the second image depicted below) using electron microscopy. [15]

Light chain–associated renal disorders. Light micr Light chain–associated renal disorders. Light microscopy (hematoxylin and eosin stain at 25X power) showing nodular glomerulosclerosis (arrow) and thickening of the basement membrane. Courtesy of Madeleine Moussa, MD, FRCPC, Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.
Light chain–associated renal disorders. Immunofluo Light chain–associated renal disorders. Immunofluorescence (25X power) showing deposits of monotypic light chain along the basement membrane. Courtesy of Madeleine Moussa, MD, FRCPC, Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.

Dense granular deposits on the endothelial side of the glomerular basement membrane (as depicted in the first, second, and third images below), on the outer aspect of the tubular basement membrane, or on both may be seen with electron microscopy in persons with LCDD. Classic ultrastructure examination findings include amorphous, noncongophilic, and nonfibrillar deposits. Most of these deposits are of kappa light chains (see the fourth image shown below). At times, the histologic changes are minimal, and occasionally glomeruli may have mesangial deposits. Rarely, glomerular crescents can also be seen in patients with LCDD.

Light chain–associated renal disorders. Immunofluo Light chain–associated renal disorders. Immunofluorescence (25X power) showing deposits of monotypic light chain along the basement membrane. Courtesy of Madeleine Moussa, MD, FRCPC, Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.
Light chain–associated renal disorders. Ultrastruc Light chain–associated renal disorders. Ultrastructure (electron microscopy at 29,000X power) showing deposition of nonfibrillar electron-dense material in the mesangial nodule (arrow). Courtesy of Madeleine Moussa, MD, FRCPC, Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.
Light chain–associated renal disorders. Ultrastruc Light chain–associated renal disorders. Ultrastructure (electron microscopy at 29,000X power) showing deposition of nonfibrillar electron-dense material along the basement membrane (arrows). Courtesy of Madeleine Moussa, MD, FRCPC, Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.
Light chain–associated renal disorders. Immunoelec Light chain–associated renal disorders. Immunoelectron microscopy (immunogold at 29,000X power) showing kappa light-chain deposition. Courtesy of Madeleine Moussa, MD, FRCPC, Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.

Because many patients with LCDD do not have overt myeloma or any other evidence of monoclonal plasma cell proliferation, they may present with renal disease manifesting with proteinuria, renal insufficiency, or renal failure. Therefore, the renal biopsy findings may provide the first clues to the diagnosis of a monoclonal gammopathy.

Immunoglobulin light-chain amyloidosis (AL)

Renal involvement is common in AL amyloidosis. In contrast to LCDD, in which the deposits are usually kappa light chains, the light chains involved in the formation of amyloidosis are usually of the lambda type. The histologic appearance of amyloid is usually quite distinctive and is confirmed easily using Congo red stains or by the ultrastructural demonstration of characteristic fibrils. AA amyloid loses its Congo red positivity when briefly exposed to potassium permanganate, while non-AA amyloid resists this treatment. In the kidney, a diagnosis of non-AA amyloidosis strongly suggests light-chain amyloidosis (AL).

Kappa light-chains are more likely to produce tubular dysfunction (Fanconi syndrome) and nodular nonamyloidotic glomerulosclerosis, while lambda light chains are more likely to be involved in the development of AL amyloidosis.

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