Pathogenesis and treatment of renal failure in multiple myeloma

Abstract

Renal failure is a frequent complication in patients with multiple myeloma (MM) that causes significant morbidity. In the majority of cases, renal impairment is caused by the accumulation and precipitation of light chains, which form casts in the distal tubules, resulting in renal obstruction. In addition, myeloma light chains are also directly toxic on proximal renal tubules, further adding to renal dysfunction. Adequate hydration, correction of hypercalcemia and hyperuricemia and antimyeloma therapy should be initiated promptly. Recovery of renal function has been reported in a significant proportion of patients treated with conventional chemotherapy, especially when high-dose dexamethasone is also used. Severe renal impairment and large amount of proteinuria are associated with a lower probability of renal recovery. Novel agents, such as thalidomide, bortezomib and lenalidomide, have significant activity in pretreated and untreated MM patients. Although there is limited experience with thalidomide and lenalidomide in patients with renal failure, data suggest that bortezomib may be beneficial in this population. Clinical studies that have included newly diagnosed and refractory patients indicate that bortezomib-based regimens may result in rapid reversal of renal failure in up to 50% of patients and that full doses of bortezomib can be administered without additional toxicity.

Urinary Albumin Excretion Patterns of Patients with Cast Nephropathy and Other Monoclonal Gammopathy–Related Kidney Diseases

“…For patients with AL and LCDD, renal biopsies were obtained to evaluate the proteinuria, which is a common accepted practice (25). However, renal biopsy has not been universally adopted for evaluation of ARF in multiple myeloma (26). In fact, the largest randomized trial for ARF in multiple myeloma was conducted with few renal biopsies (16).…”

Kidney Disease and Multiple Myeloma

“…These agents have complex mechanisms of action that include the interruption of myeloma cell growth and disruption of myeloma and bone marrow stromal cell interactions (75,76). Lenalidomide needs to be used with caution in the setting of CKD, and dose reduction is mandatory, because the drug is renally cleared.…”

Decreased HDL-Dependent Paraoxonase and Arylesterase Enzyme Activity May Indicate a Worse Prognosis in Multiple Myeloma

“…The prognosis for patients with normal renal function is better than that for those with MM and AKI. This relates to the seriousness of AKI at time of diagnosis, such that those who require and receive dialysis treatment have a median survival of less than 12 months (Augustson et al, 2008;Dimopoulos et al, 2008).…”