Clinicopathologic predictors of renal outcomes in light chain cast nephropathy: a multicenter retrospective study

Virginie Royal;Nelson Leung;Stephan Troyanov;Samih H. Nasr;Laure Ecotiere;Richard LeBlanc;Benjamin A. Adam;Andrea Angioi;Mariam P. Alexander;Anna Maria Asunis;Antonella Barreca;Paola Bianco;Camille Cohen;Maria E. Drosou;Huma Fatima;Roberta Fenoglio;François Gougeon;Jean-Michel Goujon;Guillermo A. Herrera;Bertrand Knebelmann;Nicola Lepori;Francesca Maletta;Rita Manso;Shveta S. Motwani;Antonello Pani;Marion Rabant;Helmut G. Rennke;Dario Rocatello;Frida Rosenblum;Paul W. Sanders;Afonso Santos;Karina Soto;Banu Sis;Guy Touchard;Christopher P. Venner;Frank Bridoux

2020-01-01

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Abstract

Light chain cast nephropathy (LCCN) in multiple myeloma often leads to severe and poorly reversible acute kidney injury. Severe renal impairment influences the allocation of chemotherapy and its tolerability; it also affects patient survival. Whether renal biopsy findings add to the clinical assessment in predicting renal and patient outcomes in LCCN is uncertain. We retrospectively reviewed clinical presentation, chemotherapy regimens, hematologic response, and renal and patient outcomes in 178 patients with biopsy-proven LCCN from 10 centers in Europe and North America. A detailed pathology review, including assessment of the extent of cast formation, was performed to study correlations with initial presentation and outcomes. Patients presented with a mean estimated glomerular filtration rate (eGFR) of 13 +/- 11 mL/min/1.73 m(2), and 82% had stage 3 acute kidney injury. The mean number of casts was 3.2/mm(2) in the cortex. Tubulointerstitial lesions were frequent: acute tubular injury (94%), tubulitis (82%), tubular rupture (62%), giant cell reaction (60%), and cortical and medullary inflammation (95% and 75%, respectively). Medullary inflammation, giant cell reaction, and the extent of cast formation correlated with eGFR value at LCCN diagnosis. During a median follow-up of 22 months, mean eGFR increased to 43 +/- 30 mL/min/1.73 m(2). Age, beta(2)-microglobulin, best hematologic response, number of cortical casts per squaremillimeter, and degree of interstitial fibrosis/tubular atrophy (IFTA) were independently associated with a higher eGFR during follow-up. This eGFR value correlated with overall survival, independently of the hematologic response. This study shows that extent of cast formation and IFTA in LCCN predicts the quality of renal response, which, in turn, is associated with overall survival.