15th July 2024

Multiple Myeloma & Renal Disease

Background

Renal failure is present in around 40% of patients at the time of diagnosis of multiple myeloma, with approximately an additional 20% developing it later in the course of the disease.  It is a serious complication associated with a higher rate of mortality in multiple myeloma and may occur both acutely and chronically. Proteinuria and a raised blood creatinine are the most commonly noted features, though occasionally nephrotic syndrome is seen.

Pathophysiology

There are myriad mechanisms by which renal damage may occur. The most common is cast nephropathy, where excess urinary free IgG light chains aggregate with Tamm-Horsfall proteins in the distal tubules leading to local atrophy and fibrosis.  In addition, hypercalcaemia secondary to increased bone resorption increases the incidence of nephrocalcinosis. Another mechanism includes immunoglobulin and free light chain deposition (and/or amyloid proteins) which may have direct toxic effects or contribute to glomerular damage.

It should be remembered that a number of additional factors may be present that could exacerbate renal failure in myeloma patients:

• volume depletion
• NSAIDs for pain control
• chemotherapy agents
• bisphosphonate use

Diagnosis

Although readily suspected in patients with known multiple myeloma, monoclonal-gammopathy associated with nephropathy should be included in the differential diagnosis of any patient presenting with renal failure.  The diagnosis can only be made definitively with a kidney biopsy but is often simply established by a raised creatinine, reduced creatinine clearance and identifying the presence of a monoclonal protein in the urine as well as ruling out other causes. Light chain casts will have an eosinophilic appearance on haematoxylin and eosin stain and a pale pink appearance on periodic acid-Schiff staining.

Treatment

Initially, treatment should be centred on correcting volume depletion and electrolyte imbalances if present. Nephrotoxic agents should be withheld, particularly loop diuretics as they may precipitate cast formation. NICE recommends commencing a Bortezomib and Dexamethasone combination regimen for those with untreated newly diagnosed renal failure caused by multiple myeloma.

Ultimately, the treatment of myeloma related nephropathy hinges on the reduction of the paraprotein burden by chemotherapy.  In extreme circumstances, there may be a role for plasma exchange.

References

• National Institute for Health and Care Excellence. Myeloma: Diagnosis and Management. London: NICE; 2016 Feb. (NICE Guideline No. 35.) Available from: www.nice.org.uk/guidance/ng35
• Dimopoulos MA, Sonneveld P, Leung N, Merlini G, Ludwig H, Kastritis E, Goldschmidt H, Joshua D, Orlowski RZ, Powles R, Vesole DH, Garderet L, Einsele H, Palumbo A, Cavo M, Richardson PG, Moreau P, San Miguel J, Rajkumar SV, Durie BG, Terpos E. International Myeloma Working Group Recommendations for the Diagnosis and Management of Myeloma-Related Renal Impairment. J Clin Oncol. 2016 May 1;34(13):1544-57. doi: 10.1200/JCO.2015.65.0044. Epub 2016 Mar 14. PMID: 26976420
• Korbet SM, Schwartz MM. Multiple Myeloma. Journal of the American Society of Nephrology. 2006 Sept; 17(9): 2533 – 2545
• Sive J, Cuthill K, Hunter H, Kazmi M, Pratt G, Smith D; British Society of Haematology. Guidelines on the diagnosis, investigation and initial treatment of myeloma: a British Society for Haematology/UK Myeloma Forum Guideline. Br J Haematol. 2021 Apr;193(2):245-268. doi: 10.1111/bjh.17410. Epub 2021 Mar 21. PMID: 33748957
• Kostopoulou M, Fanouriakis A, Cheema K, Boletis J, Bertsias G, Jayne D, Boumpas DT. Management of lupus nephritis: a systematic literature review informing the 2019 update of the joint EULAR and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations. RMD Open. 2020 Jul;6(2):e001263. doi: 10.1136/rmdopen-2020-001263. PMID: 32699043; PMCID: PMC7425195