Kidney disease in multiple myeloma

Renal disease is a frequent complication of symptomatic multiple myeloma, that increases morbidity and reduces quality of life and overall survival. It may result from various lesions, the most frequent being light chain cast nephropathy (LCCN), related to precipitation of monoclonal free light chains (FLC) with uromodulin in distal tubules. Rapid identification of the type of kidney disease with appropriate management is key. LCCN typically reveals the underlying myeloma and manifests with severe acute kidney injury, high serum FLC level (>500 mg/l) and predominant light chain proteinuria (urine albumin/creatinine ratio <10%). Urgent therapy is required, based on vigorous fluid expansion, correction of precipitating factors and introduction of efficient anti-myeloma therapy which choice should consider renal elimination of each agent and patient frailty. Early and deep reduction in serum FLC level conditions renal recovery, warranting assessment of efficacy by serial serum FLC level monitoring. In newly diagnosed patients, the combination of bortezomib, high-dose dexamethasone and an anti-CD38 monoclonal antibody is commonly used. The benefit to risk balance of quadruplets incorporating cyclophosphamide or an immunodulatory agent requires to be evaluated in prospective studies. In patients with severe acute kidney injury, reinforcing chemotherapy with FLC removal through plasma exchange or high-cutoff hemodialysis may increase the probability of renal response, despite controversial data from randomized trials. Histological assessment of the extent of cast formation and interstitial fibrosis/tubular atrophy may help evaluating renal prognosis and refining therapy. Thanks to improved overall survival, renal transplantation may be considered in selected candidates with end-stage kidney disease.