@article{ba0c7eef930043c08a83f47111745298,
title = "Estimated GFR Slope Across CKD Stages in Primary Hyperoxaluria Type 1",
abstract = "Rationale & Objective: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder of glyoxylate metabolism that results in early-onset kidney stone disease, nephrocalcinosis, and kidney failure. There is an unmet need for reliable markers of disease progression to test effectiveness of new treatments for patients with PH. In this study, we assessed the rate of estimated glomerular filtration rate (eGFR) decline across chronic kidney disease (CKD) glomerular filtration rate (GFR) categories (CKD G2-G5) in a cohort of patients with PH1. Study Design: Retrospective observational study. Setting & Participants: Patients with PH1 enrolled in the Rare Kidney Stone Consortium (RKSC) registry who did not have kidney failure at diagnosis and who had at least 2 eGFR values recorded from within 1 month of diagnosis until their last contact date or incident kidney failure event. Predictors: CKD GFR category, baseline patient and laboratory characteristics. Outcome: Annualized rate of eGFR decline. Analytical Approach: Generalized estimating equations and linear regression were used to evaluate the associations between CKD GFR category, baseline patient and laboratory characteristics, and annual change in eGFR during follow-up. Results: Compared with the slope in CKD G2 (−2.3 mL/min/1.73 m2 per year), the mean annual eGFR decline was nominally steeper in CKD G3a (−5.3 mL/min/1.73 m2 per year) and statistically significantly more rapid in CKD G3b and G4 (−14.7 and −16.6 mL/min/1.73 m2 per year, respectively). In CKD G2, older age was associated with a more rapid rate of eGFR decline (P = 0.01). A common PH1-causing variant of alanine glyoxylate aminotransferase, a glycine to arginine substitution at amino acid 170 (G170R), appeared to be associated with less severe annual decline in eGFR. Limitations: Data at regular time points were not available for all patients due to reliance on voluntary reporting in a retrospective rare disease registry. Conclusions: The eGFR decline was not uniform across CKD GFR categories in this PH1 population, with a higher rate of eGFR decline in CKD G3b and G4. Thus, CKD GFR category needs to be accounted for when analyzing eGFR change in the setting of PH1.",
keywords = "CKD progression, Chronic kidney disease (CKD), PH1, eGFR slope, eGFR trajectory, estimated glomerular filtration rate (eGFR), kidney failure, kidney stone, nephrocalcinosis, plasma oxalate, primary hyperoxaluria (PH), renal function, surrogate end point, urinary oxalate",
author = "Prince Singh and Vaughan, {Lisa E.} and Schulte, {Phillip J.} and Sas, {David J.} and Milliner, {Dawn S.} and Lieske, {John C.}",
note = "Funding Information: Dr Milliner has received consulting fees from OxThera, Dicerna, Allena, Alynam, and Synlogic, and grant support from the NIDDK, OxThera, Dicerna, and Alnylam. Dr Lieske has received consulting fees from the American Board of Internal Medicine, Alnylam, OxThera, Dicerna, Synlogoic, Orfan, and Novobiome, and grant support from Alnylam, Allena, Retrophin, OxThera, NIDDK, and Dicerna. Dr Sas has received consulting fees from Advicenne and lecture fees from Retrophin. Dr Singh has received an honorarium from Deerfield Institute. Dr Schulte has received consulting fees from OxThera. Ms Vaughan declares that she has no relevant financial interests. Funding Information: Prince Singh, MBBS, Lisa E. Vaughan, MS, Phillip J. Schulte, PhD, David J. Sas, DO, Dawn S. Milliner, MD, and John C. Lieske, MD. Study design: DSM, JCL, LEV; data acquisition: DSM, LEV; statistical analyses: LEV, PJS; data interpretation: DSM, JCL, LEV, PJS, PS, DJS; supervision and funding acquisition: DSM, JCL. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual's own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate. This work was funded by the Rare Kidney Stone Consortium, which is part of Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), and is funded through collaboration between NCATS and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; grant U54DK83908). This work was also supported by funds form the Oxalosis and Hyperoxaluria Foundation, Mayo Foundation, and an industry grant from OxThera, Inc. Those funding the study had no role in study design, analysis, reporting, or the decision to submit the manuscript for publication. Dr Milliner has received consulting fees from OxThera, Dicerna, Allena, Alynam, and Synlogic, and grant support from the NIDDK, OxThera, Dicerna, and Alnylam. Dr Lieske has received consulting fees from the American Board of Internal Medicine, Alnylam, OxThera, Dicerna, Synlogoic, Orfan, and Novobiome, and grant support from Alnylam, Allena, Retrophin, OxThera, NIDDK, and Dicerna. Dr Sas has received consulting fees from Advicenne and lecture fees from Retrophin. Dr Singh has received an honorarium from Deerfield Institute. Dr Schulte has received consulting fees from OxThera. Ms Vaughan declares that she has no relevant financial interests. We thank all patients and families who have participated in the RKSC PH registry as well as the many physicians who collected detailed clinical records. Further, we thank the study coordinators who collected the clinical data and biological samples and particularly thank referring nephrologists Drs Baum, Greenbaum, Saland, Bartosh, and Chandra. Aspects of this work were presented in abstract form at the ISN World Congress of Nephrology, held virtually April 15-19, 2021. Received June 18, 2021. Evaluated by 3 external peer reviewers, with direct editorial input from a Statistics/Methods Editor, an Associate Editor, and the Editor-in-Chief. Accepted in revised form January 14, 2022. Funding Information: This work was funded by the Rare Kidney Stone Consortium, which is part of Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), and is funded through collaboration between NCATS and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; grant U54DK83908). This work was also supported by funds form the Oxalosis and Hyperoxaluria Foundation, Mayo Foundation, and an industry grant from OxThera, Inc. Those funding the study had no role in study design, analysis, reporting, or the decision to submit the manuscript for publication. Publisher Copyright: {\textcopyright} 2022 National Kidney Foundation, Inc.",
year = "2022",
month = sep,
doi = "10.1053/j.ajkd.2022.01.428",
language = "English (US)",
volume = "80",
pages = "373--382",
journal = "American Journal of Kidney Diseases",
issn = "0272-6386",
publisher = "W.B. Saunders Ltd",
number = "3",
}