Citations 3
Evidence Supporting Light Chain Cast Nephropathy As a Myeloma Defining Event
Angioi, Andrea , Cohen, Camille , Duriseti, Parikshit , Fonder, Amie , Hayman, Suzanne R. , Hobbs, Miriam, Hwa, Yi L. , Kapoor, Prashant , Knebelmann, Bertrand , Kourelis, Taxiarchis , Kumar, Shaji , Kyle, Robert A. , Lacy, Martha Q. , Lepori, Nicola , Lin, Yi , Motwani, Shveta S. , Nasr, Samih H. , Royal, Virginie , Troyanov, Stéphan , Venner, Christopher P. , Warsame, Rahma , Yarandi, Niloufarsadat, Binder, Moritz , Leung, Nelson , Bridoux, Frank , Dingli, David , Dispenzieri, Angela , Fenoglio, Roberta , Gertz, Morie A. , Go, Ronald S. , Gonsalves, Wilson I. , Muchtar, Eli , Pani, Antonello , Roccatello, Dario , Sanders, Paul W. , Rajkumar, S. Vincent
Blood | November 28, 2022 | Volume: 140 | Issue: Supplement 1 | Pages: 10068-10070
Clinicopathologic predictors of renal outcomes in light chain cast nephropathy: a multicenter retrospective study
Royal, Virginie , Leung, Nelson , Troyanov, Stéphan , Nasr, Samih H. , Écotière, Laure, LeBlanc, Richard , Adam, Benjamin , Angioi, Andrea , Alexander, Mariam P., Asunis, Anna Maria, Barreca, Antonella , Cohen, Camille , Drosou, Maria Eleni , Fatima, Huma , Gougeon, F. , Goujon, Jean‐Michel, Herrera, Guillermo A. , Knebelmann, Bertrand , Lepori, Nicola , Manso, Rita , Motwani, Shveta S. , Pani, Antonello , Rabant, Marion , Rennke, Helmut G. , Rocatello, Dario, Rosenblum, Frida , Sanders, Paul W. , Santos, Afonso , Soto, Karina , Sis, B. , Touchard, Guy, Venner, Christopher P. , Bridoux, Frank , Drosou, Maria E, Leung, Nelson , Bianco, Paola, Fenoglio, Roberta , Gougeon, François, Maletta, Francesca
Blood | March 11, 2020 | Volume: 135 | Issue: 21 | Pages: 1833-1846
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 m2, and 82% had stage 3 acute kidney injury. The mean number of casts was 3.2/mm2 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 m2. Age, β2-microglobulin, best hematologic response, number of cortical casts per square millimeter, 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.
The longitudinal relationship between patient-reported outcomes and clinical characteristics among patients with focal segmental glomerulosclerosis in the Nephrotic Syndrome Study Network
Troost, Jonathan P. , Waldo, Anne, Carlozzi, Noelle E. , Murphy, Shannon L., Modersitzki, Frank , Trachtman, Howard , Nachman, Patrick H. , Reidy, Kimberly J. , Selewski, David T. , Herreshoff, Emily, Srivastava, Tarak, Gibson, Keisha L. , Derebail, Vimal K. , Lin, Jen Jar, Hingorani, Sangeeta, Sambandam, Kamalanathan K. , Athavale, Ambarish M., Reich, Heather N. , Adler, Sharon G. , Dell, Katherine M., Appel, Gerald B., Wang, Chia-shi , Kaskel, Frederick J. , Lafayette, Richard , Atkinson, Meredith A. , Kretzler, Matthias , Lemley, Kevin V. , Brown, Elizabeth , Meyers, Kevin , Gadegbeku, Crystal A., Holzman, Lawrence B. , Jefferson, Jonathan Ashley, Tuttle, Katherine R, Singer, Pamela, Hogan, Marie C. , Cattran, Daniel C., Network, the Nephrotic Syndrome Study, Dell, K, Schachere, M., Lemley, K, Whitted, L, Haney, Connie J, Gurusinghe, Sayuri , Toledo, Michelly Louise Sartório Altoé, Greenbaum, L, Wang, C, Lee, B, Nast, Cynthia C. , Page, J La, Stroger, John H, Itteera, M. , Neu, Alicia M. , Boynton, Sara Ashley, Chernitskiy, Vladimir, Reidy, K, Kopp, J, Castro-Rubio, E, Brede, E, Blake, J. Thomas, Modersitzki, F, Lafayette, R, Mehta, K. , Johnstone, Duncan B., Pfeffer, Zoe, Cattran, D, Hladunewich, M, Reich, H, Ling, P., Romano, M, Barisoni, L, Bidot, Carlos, Kretzler, M, Williams, A, Pitter, R, Gibson, K, Grubbs, S, Froment, Anne, Holzman, L, Kallem, K., Cerecino, F J, Johnson, N, Jefferson, A, Tuttle, Katherine R. , Klepach, K, Kelton, M, Cooper, Ann , Lin, J J, Spainhour, Mitzie, Gray, S, Barisoni, L, Gillespie, B, Gipson, D, Holzman, L, Mariani, Laura , Song, Peter X.‐K. , Kincaid, Colleen, Lienczewski, Chrysta, Mainieri, T, Williams, Anna , Ávila-Casado, Carmen , Bagnasco, Serena M. , Gaut, Joseph P. , Hewitt, Stephen M. , Palmer, M, Rosenberg, A, Royal, Virginie , Barisoni, L, Nast, C, Roy, Cindy N., Urv, T, Dell, K, Greenbaum, L, Lee, B, Page, J La, Stroger, John H, Reidy, K, Kopp, J, Brede, E, Modersitzki, F, Lafayette, R, Gadegbeku, C, Cattran, D, Hladunewich, M, Reich, H, Romano, M, Pitter, R, Gibson, K, Cerecino, F J, Jefferson, A, Lin, J J, Gray, S, Kretzler, M, Gillespie, B, Gipson, D, Mariani, L, Mainieri, T, Williams, A, Mariani, L, Palmer, M, Rosenberg, A, Barisoni, L, Urv, T, Wang, Chia-Shi , Tuttle, Katherine R , Hogan, Marie C , Fornoni, Alessia , Fervenza, Fernando C. , Kopp, Jeffrey B. , Greenbaum, Larry A. , Sedor, John R. , Lieske, John C. , Srivastava, Tarak , Hladunewich, Michelle , Tuttle, Katherine R, Singer, Pamela S. , Barisoni, Laura , Gipson, Debbie S , Network, the Nephrotic Syndrome Study, Dell, K, Lemley, K, Greenbaum, L, Lee, B, Page, J La, Stroger, John H, Reidy, K, Kopp, J, Brede, E, Zhdanova, Olga A. , Modersitzki, F, Vento, Sandro , Lafayette, R, Cattran, D, Hladunewich, M, Reich, H, Romano, M, Barisoni, L, Bidot, C, Kretzler, M, Williams, A, Pitter, R, Gibson, K, Holzman, L, Cerecino, F J, Jefferson, A, Freedman, Barry I. , Lin, J J, Gray, S, Barisoni, L, Gillespie, B, Gipson, D, Holzman, L, Sampson, Matthew Gordon , Zee, Jarcy , Mainieri, T, Hodgin, Jeffrey B. , Palmer, M, Rosenberg, A, Thomas, D, Barisoni, L, Nast, C, Abbott, Kevin C. , Roy, C, Urv, T, Brooks, Philip John , Dell, K, Greenbaum, L, Lee, B, Page, J La, Stroger, John H, Reidy, K, Kopp, J, Brede, E, Modersitzki, F, Lafayette, R, Gadegbeku, C, Cattran, D, Hladunewich, M, Reich, H, Romano, M, Bidot, C, Pitter, R, Gibson, K, Cerecino, F J, Jefferson, A, Lin, J J, Gray, S, Kretzler, M, Gillespie, B, Gipson, D, Mariani, L, Mainieri, T, Williams, A, Mariani, L, Palmer, M, Rosenberg, A, Thomas, D, Barisoni, L, Roy, C, Urv, T, Troost, Jonathan P.
Clinical Kidney Journal | July 3, 2019 | Volume: 13 | Issue: 4 | Pages: 597-606
Abstract Background Understanding the relationship between clinical and patient-reported outcomes (PROs) will help support clinical care and future clinical trial design of novel therapies for focal segmental glomerulosclerosis (FSGS). Methods FSGS patients ≥8 years of age enrolled in the Nephrotic Syndrome Study Network completed Patient-Reported Outcomes Measurement Information System PRO measures of health-related quality of life (HRQoL) (children: global health, mobility, fatigue, pain interference, depression, anxiety, stress and peer relationships; adults: physical functioning, fatigue, pain interference, sleep impairment, mental health, depression, anxiety and social satisfaction) at baseline and during longitudinal follow-up for a maximum of 5 years. Linear mixed-effects models were used to determine which demographic, clinical and laboratory features were associated with PROs for each of the eight children and eight adults studied. Results There were 45 children and 114 adult FSGS patients enrolled that had at least one PRO assessment and 519 patient visits. Multivariable analyses among children found that edema was associated with global health (−7.6 points, P = 0.02) and mobility (−4.2, P = 0.02), the number of reported symptoms was associated with worse depression (−2.7 per symptom, P = 0.009) and anxiety (−2.3, P = 0.02) and the number of emergency room (ER) visits in the prior 6 months was associated with worse mobility (−2.8 per visit, P < 0.001) and fatigue (−2.4, P = 0.03). Multivariable analyses among adults found the number of reported symptoms was associated with worse function in all eight PROMIS measures and the number of ER visits was associated with worse fatigue, pain interference, sleep impairment, depression, anxiety and social satisfaction. Laboratory markers of disease severity (i.e. proteinuria, estimated glomerular filtration rate and serum albumin) did not predict PRO in multivariable analyses, with the single exception of complete remission and better pain interference scores among children (+9.3, P = 0.03). Conclusions PROs provide important information about HRQoL for persons with FSGS that is not captured solely by the examination of laboratory-based markers of disease. However, it is critical that instruments capture the patient experience and FSGS clinical trials may benefit from a disease-specific instrument more sensitive to within-patient changes.