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Prolonged renal survival in light chain amyloidosis: speed and magnitude of light chain reduction is the crucial factor

Rezk, T; Lachmann, HJ; Fontana, M; Sachchithanantham, S; Mahmood, S; Petrie, A; Whelan, CJ; ... Gillmore, JD; + view all (2017) Prolonged renal survival in light chain amyloidosis: speed and magnitude of light chain reduction is the crucial factor. Kidney International , 92 (6) pp. 1476-1483. 10.1016/j.kint.2017.05.004. Green open access

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Abstract

Renal involvement causing progressive chronic kidney disease (CKD) is present in 70% of patients with systemic Ig light-chain (AL) amyloidosis at diagnosis. Chemotherapy that substantially suppresses free light chain production is associated with improved patient survival, but its benefit in delaying the onset of renal replacement therapy among patients who present with established advanced CKD has not been studied. To evaluate this, we studied 1000 patients enrolled in the prospective UK AL amyloidosis chemotherapy study (ALchemy). Of these, 84 patients had advanced amyloid-related CKD defined by an estimated glomerular filtration rate (eGFR) under 20 ml/min/1.73 m(2). We determined outcomes among these 84 patients, who had a median eGFR of 10 ml/min/1.73 m(2), in relation to response to chemotherapy evaluated at three, six, and 12 months from baseline. Patients who achieved suppression of 90% or more in their amyloidogenic free light chain (dFLC) within three months of baseline had significantly better overall survival, prolonged time to dialysis, and prolonged time to the composite endpoint of 'death or dialysis' compared to those who achieved lesser degrees of clonal response at the same time point. Even when this target of greater than 90% dFLC response was achieved but was delayed beyond 3 months, it was associated with worse outcomes. Cox regression analyses confirmed that a 90% or better dFLC response within 3 months was the only significant independent predictor of all three of these outcome measures. Thus, renal survival among patients with systemic immunologic light chain amyloidosis who present with advanced CKD is strongly dependent upon the magnitude and speed with which the underlying hematologic disorder is suppressed by chemotherapy.

Type: Article
Title: Prolonged renal survival in light chain amyloidosis: speed and magnitude of light chain reduction is the crucial factor
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.kint.2017.05.004
Publisher version: https://doi.org/10.1016/j.kint.2017.05.004
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: amyloid, amyloidosis, chemotherapy, chronic kidney disease
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Nephrology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Eastman Dental Institute
URI: https://discovery.ucl.ac.uk/id/eprint/1567713
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