Light Chain-Associated Renal Disorders Treatment & Management

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

Approach Considerations

The goals of treatment are to prolong survival and to maintain quality of life.

Management of light-chain nephropathy depends on the underlying disease process. Take steps to limit further cast precipitation, and implement effective prevention and management of its complications.

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Medical Care

Proximal tubular dysfunction (Fanconi syndrome) and metabolic acidosis is treated with sodium bicarbonate therapy; hypophosphatemia requires phosphate supplementation.

Distal renal tubular acidosis is treated with sodium bicarbonate therapy. Thiazide therapy (if no hypercalcemia is present) or correct calcium level (if hypercalcemia is present) in patients with nephrogenic diabetes insipidus and distal tubular dysfunction.

Amyloidosis is treated with chemotherapy. Waldenstrom macroglobulinemia requires plasmapheresis for hyperviscosity.

Multiple myeloma

The goals of therapy in patients with multiple myeloma and renal failure are to optimize volume status; avoid and treat hypercalcemia, hyperuricemia, and infections; reduce the burden of light chains either by suppressing production with chemotherapy and/or removal of light chains with plasmapheresis or hemodialysis using high-cutoff dialyzers; and dialysis to correct complications of renal failure, as per usual indications.

Any of the following chemotherapy regimens can be used in patients with multiple myeloma:

  • Melphalan and corticosteroids

  • Combination chemotherapy - VAD (ie, vincristine, Adriamycin, dexamethasone), ABCM (ie, Adriamycin, carmustine [BiCNU], cyclophosphamide, melphalan), or MEVP (ie, melphalan, cyclophosphamide, vincristine, prednisone) [16]

  • Bortezomib, thalidomide, dexamethasone, doxorubicin

  • Interferon alfa 2b

Autologous stem cell transplantation, allogenic or autologous

Myeloablative high-dose chemotherapy and autologous stem cell transplantation induce hematologic remission in a high proportion of patients who are eligible for such treatment, and early results from a limited number of patients suggest that the deterioration of renal function may be arrested and possibly reversed. [17]

Stem cell transplant (SCT) is recommended for light chain proximal tubulopathy (LCPT) to delay renal progression and to minimize the risk of recurrence after renal transplantation. Stokes and colleagues reported on outcomes of 46 patients with LCPT treated between 2000 and 2014. Complete or very good partial hematologic remissions were achieved in one-third of treated patients, with lowest mortality and best hematologic outcomes seen in patients receiving SCT. [18]  

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Rare Causes of Acute Renal Failure

Tumor lysis syndrome

Uric acid released following chemotherapy may precipitate in the tubules and may precipitate acute renal failure. Hence, pretreating patients undergoing chemotherapy with allopurinol and diuresis is important.

Nephrolithiasis and urinary tract infections

Infections of the upper and lower urinary tract are common in patients with multiple myeloma because of suppression of humoral immunity. Treat nephrolithiasis and urinary tract infections promptly.

Hyperviscosity

Measure plasma viscosity in patients with clinical features of hyperviscosity. Urgent plasmapheresis is required in such patients.

Myeloma cell infiltration

Treat the underlying process.

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Treatment of Renal Failure

Patients with renal failure should have early, permanent vascular access because of the high risk of infection associated with temporary catheters. Refer the patient to a vascular surgeon for the placement of a permanent vascular access device.

Institute dialysis early to avoid uremia compounding the complications of underlying disease. Approximately 20% of patients die within the first month, but predicting which patients will die is not possible. Because 50% of the survivors live longer than 1 year and because recovery of renal function is often delayed for several months, a policy of offering dialysis to most patients is justified. All patients with myeloma who present with acute renal failure should receive dialysis.

Long-term dialysis (hemodialysis or peritoneal dialysis) should be considered for patients with chronic renal failure and myeloma who are responsive to chemotherapy. Before instituting long-term dialysis therapy, consider the extent of other systemic disease. Patients who have progressive myeloma and do not respond to chemotherapy may not be candidates for long-term dialysis because their prognosis is very poor.

Plasmapheresis

The strong association between light-chain excretion and renal failure suggests that light chains play a primary pathogenetic role in producing kidney damage. Plasma exchange appears to be the most efficient way to rapidly remove large amounts of light chains and has been advocated by many over the last 15 years, but its efficacy has not been established convincingly.

Zucchelli et al reported significantly higher survival rates in patients treated with plasma exchange (66% vs 28%, P< .001). [19] In another randomized prospective trial, Johnson et al found no significant difference in the number of patients whose renal function improved with this therapy; however, they noted that patients with severe renal failure improved with plasma exchange. [20]

Clarke et al [21] found no statistically significant difference in the outcomes in a randomized controlled trial; however, this trial had several limitations as there was substantial uncertainty regarding the diagnosis of cast nephropathy because only 61% of the patients had light chains in urine. [22] A retrospective analysis of patients with a diagnosis of cast nephropathy with monitoring of serum light chains to guide therapy showed benefit for plasmapheresis in almost three quarters of the patients, [23] but the benefit of the published data is inconclusive and a well-designed prospective trial is recommended in the future. [24] Complete renal recovery was observed in 40% of patients with early institution of plasmapheresis and bortezomib-based chemotherapy to treat myeloma. [25]

Early and aggressive therapy with 5-7 exchanges within 7-10 days is recommended, and the duration of therapy should be guided by serum free light chains with the aim to reduce light chains by a minimum of 60% for recovery of renal function. [26] Plasmapheresis should be performed in conjunction with dexamethasone and bortezomib-based chemotherapy to reduce light chain production.

High-cutoff dialyzers

Removal of serum free light chains with large-pore (25-50 kd) dialyzers rather than standard high-flux dialyzers has been demonstrated in a pilot study of 19 patients with biopsy proven myeloma kidney, in which 13 of the patients became dialysis-independent within 27 days [27] and 2 trials—European Trial of Free Light Chain Removal by Extended Hemodialysis in Cast Nephropathy (EuLITE) and Studies in patients with Multiple Myeloma and Renal Failure due to Myeloma Cast Nephropathy (MYRE)—are ongoing in Europe to further assess the efficacy of these high-cutoff dialyzers in myeloma kidney failure. In a recent report, by the original authors, high-cutoff dialyzers were found to be ineffective in removing free light chains due to formation of large FLC aggregates. [28]

Transplantation

Transplantation has been performed successfully in patients with end-stage renal disease secondary to multiple myeloma. Consider renal transplantation only in patients who have achieved hematologic remission and who have no other major complications of their monoclonal gammopathy. Recurrent disease is common in patients with LCDD following transplantation, and renal transplantation should not be done until optimal measures have ensured substantial reduction in light chain production.

Other

Treat infection early and effectively with nonnephrotoxic antibiotics. Intravenous immunoglobulin infusions have been used as prophylaxis against infection in the plateau phase of the disease.

Hyperviscosity may manifest as confusion and neurological symptoms. Measure plasma viscosity in these patients, and implement urgent plasmapheresis.

Provide sodium bicarbonate supplementation to effectively control acidosis.

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Consultations

A multidisciplinary approach is important in the treatment of these patients, and consultations with following specialists are useful:

  • Hematologist/oncologist - Treatment of the underlying disease process

  • Nephrologist - Prevention and treatment of acute and chronic renal failure

  • Infectious disease specialist - Treatment of sepsis in immunocompromised patients

  • Blood purification specialist - Plasmapheresis

  • Vascular surgeon - Placement of a permanent vascular access device for dialysis

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Diet

No special restrictions are required unless the patient has chronic renal failure.

  • Optimize nutritional intake.

  • High fluid intake (2-3 L/d) is important to avoid dehydration and to minimize further cast formation.

  • Increased fluid intake is important during periods of volume depletion (eg, fever, diarrhea, vomiting).

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Prevention

Maintain adequate fluid intake (2-3 L/d), especially before initiating chemotherapy, to prevent dehydration.  Dehydration and aciduria favors precipitation of light chains. This is important in the precipitation of acute renal failure in a significant number (up to 95%) of patients. 

Avoid nephrotoxic agents. NSAIDs, often used to relieve bone pain, are the most prominent offenders.

Ensure early and effective treatment of infections with nonnephrotoxic antibiotics. Intravenous immunoglobulin has been found to be safe when used as prophylaxis against infection in the so-called plateau phase.

Early recognition and treatment of hypercalcemia are important. Excessive calcium is an important cause of acute renal failure in patients with myeloma and may be present in up to 30% of patients. Hypercalcemia impairs renal concentrating ability, thus leading to dehydration and promoting precipitation of light-chain proteins in renal tubules. Nausea, vomiting, and altered mental state associated with hypercalcemia further increase the likelihood of dehydration. Hypercalciuria also exerts a direct nephrotoxic effect and thus causes tubular degeneration and necrosis. Implement aggressive treatment of hypercalcemia, with saline diuresis, steroids, calcitonin, and diphosphonate.

Perform contrast studies judiciously in patients with multiple myeloma because of the possibility of contrast-induced renal failure. However, McCarthy and Becker reviewed 7 retrospective studies of patients with myeloma who were receiving contrast media and noted that the incidence rate of acute renal failure was only 0.6-1.25%, compared to 0.15% in the general population. [29]

 

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