TY - JOUR
T1 - Age of Onset and Disease Course in Biopsy-Proven Minimal Change Disease
T2 - An Analysis From the Cure Glomerulonephropathy Network
AU - CureGN Consortium
AU - Chen, Dhruti P.
AU - Helmuth, Margaret E.
AU - Smith, Abigail R.
AU - Canetta, Pietro A.
AU - Ayoub, Isabelle
AU - Mucha, Krzysztof
AU - Kallash, Mahmoud
AU - Kopp, Jeffrey B.
AU - Gbadegesin, Rasheed
AU - Gillespie, Brenda W.
AU - Greenbaum, Larry A.
AU - Parekh, Rulan S.
AU - Hunley, Tracy E.
AU - Sperati, C. John
AU - Selewski, David T.
AU - Kidd, Jason
AU - Chishti, Aftab
AU - Reidy, Kimberly
AU - Mottl, Amy K.
AU - Gipson, Debbie S.
AU - Srivastava, Tarak
AU - Twombley, Katherine E.
AU - Ahn, Wooin
AU - Appel, Gerald
AU - Appelbaum, Paul
AU - Babayev, Revekka
AU - Bomback, Andrew
AU - Chan, Brenda
AU - D'Agati, Vivette Denise
AU - Dogra, Samitri
AU - Fernandez, Hilda
AU - Gharavi, Ali
AU - Hines, William
AU - Husain, Syed Ali
AU - Jain, Namrata
AU - Kiryluk, Krzysztof
AU - Lin, Fangming
AU - Marasa, Maddalena
AU - Markowitz, Glen
AU - Rasouly, Hila Milo
AU - Mohan, Sumit
AU - Mongera, Nicola
AU - Nestor, Jordan
AU - Nickolas, Thomas
AU - Radhakrishnan, Jai
AU - Lane, Jerome
AU - Ghossein, Cybele
AU - Peleg, Yonatan
AU - Wadhwani, Shikha
AU - Krissberg, Jill
N1 - Publisher Copyright:
© 2023 National Kidney Foundation, Inc.
PY - 2023/6
Y1 - 2023/6
N2 - Rationale & Objective: Adolescent- and adult-onset minimal change disease (MCD) may have a clinical course distinct from childhood-onset disease. We characterized the course of children and adults with MCD in the Cure Glomerulonephropathy Network (CureGN) and assessed predictors of rituximab response. Study Design: Prospective, multicenter, observational study. Study Participants: CureGN participants with proven MCD on biopsy. Exposure: Age at disease onset, initiation of renin-angiotensin-aldosterone system (RAAS) blockade, and immunosuppression including rituximab during the study period. Outcome: Relapse and remission, change in estimated glomerular filtration rate (eGFR), and kidney failure. Analytical Approach: Remission and relapse probabilities were estimated using Kaplan-Meier curves and gap time recurrent event models. Linear regression models were used for the outcome of change in eGFR. Cox proportional hazards models were used to estimate the association between rituximab administration and remission. Results: The study included 304 childhood- (≤12 years old), 49 adolescent- (13-17 years old), and 201 adult- (≥18 years) onset participants with 2.7-3.2 years of follow-up after enrollment. Children had a longer time to biopsy (238 vs 23 and 36 days in adolescent- and adult-onset participants, respectively; P < 0.001) and were more likely to have received therapy before biopsy. Children were more likely to be treated with immunosuppression but not RAAS blockade. The rate of relapse was higher in childhood- versus adult-onset participants (HR, 1.69 [95% CI, 1.29-2.21]). The probability of remission was also higher in childhood-onset disease (HR, 1.33 [95%CI, 1.02-1.72]). In all groups eGFR loss was minimal. Children were more likely to remit after rituximab than those with adolescent- or adult-onset disease (adjusted HR, 2.1; P = 0.003). Across all groups, glucocorticoid sensitivity was associated with a greater likelihood of achieving complete remission after rituximab (adjusted HR, 2.62; P = 0.002). Limitations: CureGN was limited to biopsy-proven disease. Comparisons of childhood to nonchildhood cases of MCD may be subject to selection bias, given that childhood cases who undergo a biopsy may be limited to patients who are least responsive to initial therapy. Conclusions: Among patients with MCD who underwent kidney biopsy, there were differences in the course (relapse and remission) of childhood-onset compared with adolescent- and adult-onset disease, as well as rituximab response. Plain-Language Summary: Minimal change disease is a biopsy diagnosis for nephrotic syndrome. It is diagnosed in childhood, adolescence, or adulthood. Patients and clinicians often have questions about what to expect in the disease course and how to plan therapies. We analyzed a group of patients followed longitudinally as part of the Cure Glomerulonephropathy Network (CureGN) and describe the differences in disease (relapse and remission) based on the age of onset. We also analyzed rituximab response. We found that those with childhood-onset disease had a higher rate of relapse but also have a higher probability of reaching remission when compared with adolescent- or adult-onset disease. Children and all steroid-responsive patients are more likely to achieve remission after rituximab.
AB - Rationale & Objective: Adolescent- and adult-onset minimal change disease (MCD) may have a clinical course distinct from childhood-onset disease. We characterized the course of children and adults with MCD in the Cure Glomerulonephropathy Network (CureGN) and assessed predictors of rituximab response. Study Design: Prospective, multicenter, observational study. Study Participants: CureGN participants with proven MCD on biopsy. Exposure: Age at disease onset, initiation of renin-angiotensin-aldosterone system (RAAS) blockade, and immunosuppression including rituximab during the study period. Outcome: Relapse and remission, change in estimated glomerular filtration rate (eGFR), and kidney failure. Analytical Approach: Remission and relapse probabilities were estimated using Kaplan-Meier curves and gap time recurrent event models. Linear regression models were used for the outcome of change in eGFR. Cox proportional hazards models were used to estimate the association between rituximab administration and remission. Results: The study included 304 childhood- (≤12 years old), 49 adolescent- (13-17 years old), and 201 adult- (≥18 years) onset participants with 2.7-3.2 years of follow-up after enrollment. Children had a longer time to biopsy (238 vs 23 and 36 days in adolescent- and adult-onset participants, respectively; P < 0.001) and were more likely to have received therapy before biopsy. Children were more likely to be treated with immunosuppression but not RAAS blockade. The rate of relapse was higher in childhood- versus adult-onset participants (HR, 1.69 [95% CI, 1.29-2.21]). The probability of remission was also higher in childhood-onset disease (HR, 1.33 [95%CI, 1.02-1.72]). In all groups eGFR loss was minimal. Children were more likely to remit after rituximab than those with adolescent- or adult-onset disease (adjusted HR, 2.1; P = 0.003). Across all groups, glucocorticoid sensitivity was associated with a greater likelihood of achieving complete remission after rituximab (adjusted HR, 2.62; P = 0.002). Limitations: CureGN was limited to biopsy-proven disease. Comparisons of childhood to nonchildhood cases of MCD may be subject to selection bias, given that childhood cases who undergo a biopsy may be limited to patients who are least responsive to initial therapy. Conclusions: Among patients with MCD who underwent kidney biopsy, there were differences in the course (relapse and remission) of childhood-onset compared with adolescent- and adult-onset disease, as well as rituximab response. Plain-Language Summary: Minimal change disease is a biopsy diagnosis for nephrotic syndrome. It is diagnosed in childhood, adolescence, or adulthood. Patients and clinicians often have questions about what to expect in the disease course and how to plan therapies. We analyzed a group of patients followed longitudinally as part of the Cure Glomerulonephropathy Network (CureGN) and describe the differences in disease (relapse and remission) based on the age of onset. We also analyzed rituximab response. We found that those with childhood-onset disease had a higher rate of relapse but also have a higher probability of reaching remission when compared with adolescent- or adult-onset disease. Children and all steroid-responsive patients are more likely to achieve remission after rituximab.
KW - Adolescents
KW - adults
KW - age at disease onset
KW - children
KW - clinical phenotype
KW - clinical trajectory
KW - disease course
KW - eGFR change
KW - estimated glomerular filtration rate (eGFR)
KW - minimal change disease (MCD)
KW - nephrotic syndrome (NS)
KW - prognosis
KW - proteinuria
KW - relapse
KW - remission
KW - rituximab
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UR - http://www.scopus.com/inward/citedby.url?scp=85148341507&partnerID=8YFLogxK
U2 - 10.1053/j.ajkd.2022.11.012
DO - 10.1053/j.ajkd.2022.11.012
M3 - Article
C2 - 36608921
AN - SCOPUS:85148341507
SN - 0272-6386
VL - 81
SP - 695-706.e1
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 6
ER -