27.1. Renal impairment in multiple myeloma

Chapter 27

Cast nephropathy:

  • Is the principal cause of severe acute kidney injury in multiple myeloma.
  • Is the most likely diagnosis if patients present with acute kidney injury and sFLCs ≥500 mg/L.
  • Is characterised by obstruction of the distal tubules by monoclonal FLCs in association with Tamm-Horsfall protein (uromodulin).
  • Therapy can be monitored with sFLCs.
  • Renal recovery and patient survival is improved with sustained reductions in sFLCs.

Renal impairment (defined as an estimated glomerular filtration rate [eGFR] of <60 ml/min/1.73 m2) is a common and potentially serious finding in multiple myeloma (MM). It is present in up to 40% of patients at diagnosis and affects up to 50% of patients at some time during their disease [549][550]. In most cases renal impairment is reversible, being caused by treatable factors such as dehydration, hypercalcaemia or nephrotoxic drugs. However, around 3.5% of MM patients present with severe acute kidney injury (AKI) requiring dialysis [551]. For up to 90% of such patients, the underlying cause is cast nephropathy [550]. The International Myeloma Working Group (IMWG) recommend the use of quantitative sFLC values to help distinguish cast nephropathy from other renal pathologies (e.g. LCDD or AL amyloidosis) in MM patients with renal impairment (Section 25.3.7) [859]. Higher rates of renal impairment, and increased severity of renal impairment, are associated with increased sFLC concentrations [1191]. A number of studies have also shown that high levels of FLCs at MM diagnosis can also identify patients at increased risk of renal failure and worse outcome (Section 20.1) [247][953].

Severe AKI is a significant problem: MM patients account for 2% of the dialysis population, with approximately 5,000 new cases worldwide per year [552][553]. A 2010 review of the data collected from a large European registry showed that renal morbidity was a considerable burden. Of the 159,367 patients on renal replacement therapy, the median survival was 0.91 years in MM and light chain deposition disease (LCDD) (n=2,453) versus 4.46 years in non-MM patients [553]. MM patients are associated with low rates of recovery of kidney function with the majority remaining on dialysis until death [554]. Early recovery of renal function should be a therapeutic aim as median survival is increased several-fold if this is achieved [555][556], although newly-diagnosed MM patients who recover renal function still have inferior survival outcomes compared to those without renal impairment [557].

In this chapter, algorithms for screening for MM in patients presenting with AKI are reviewed together with serum free light chain (sFLC) measurements for monitoring light chain removal strategies such as plasma exchange, haemodialysis and adsorption techniques. Finally, there is some data concerning how renal recovery and patient survival can be predicted by sustained reductions in free light chains (FLCs) [551].