Portal de Periódicos da CAPES

Health-related quality of life in glomerular disease

2019; Elsevier BV; Volume: 95; Issue: 5 Linguagem: Inglês

10.1016/j.kint.2018.12.018

1523-1755

Pietro A. Canetta, Jonathan P. Troost, Shannon Mahoney, Amy J. Kogon, Noelle E. Carlozzi, Sharon Bartosh, Yi Cai, T. Keefe Davis, Hilda Fernández, Alessia Fornoni, Rasheed Gbadegesin, Emily Herreshoff, John D. Mahan, Patrick H. Nachman, David T. Selewski, Christine B. Sethna, Tarak Srivastava, Katherine R. Tuttle, Chia-shi Wang, Ronald J. Falk, Ali G. Gharavi, Brenda W. Gillespie, Larry A. Greenbaum, Lawrence B. Holzman, Matthias Kretzler, Bruce Robinson, William E. Smoyer, Lisa M. Guay‐Woodford, Bryce B. Reeve, Debbie S. Gipson, Wooin Ahn, Gerald B. Appel, Revekka Babayev, Ibrahim Batal, Andrew S. Bomback, Eric J. Brown, Eric S. Campenot, Pietro A. Canetta, Lucrezia Carlassara, Brenda Chan, Debanjana Chatterjee, Vivette D. D’Agati, Elisa Delbarba, Samriti Dogra, Hilda Fernández, Bartosz Foroncewicz, Ali G. Gharavi, Gian Marco Ghiggeri, William H. Hines, S. Ali Husain, Namrata G. Jain, Pascale Khairallah, Byum Hee Kil, Krzysztof Kiryluk, Anushya Jeyabalan, Wai Lam Lau, Fangming Lin, Francesca Lugani, Maddalena Marasà, Glen S. Markowitz, Sumit Mohan, Xueru Mu, Krzysztof Mucha, Thomas L. Nickolas, Stacy Piva, Jai Radhakrishnan, Maya K. Rao, Renu Regunathan-Shenk, Simone Sanna‐Cherchi, Dominick Santoriello, Shayan Shirazian, Michael B. Stokes, Natalie Uy, Anthony M. Valeri, Larry A. Greenbaum, William E. Smoyer, Amira Al‐Uzri, Josephine M. Ambruzs, Isa Ashoor, Diego Avilés, Rossana Baracco, John Barcia, Sharon Bartosh, Craig W. Belsha, Corinna Bowers, Michael Braun, Yi Cai, Vladimir Chernitskiy, Aftab S. Chishti, Donna Claes, Kira Clark, Carl H. Cramer, Keefe Davis, Elif Erkan, Daniel I. Feig, Michael Freundlich, Joseph P. Gaut, Rasheed Gbadegesin, Melisha Hanna, Guillermo Hidalgo, David K. Hooper, Tracy E. Hunley, Amrish Jain, Mahmoud Kallash, Margo Kamel, Myda Khalid, Jon B. Klein, Theresa Kump, Jerome C. Lane, Helen Liapis, John D. Mahan, Carla Nester, Cynthia X. Pan, Larry T. Patterson, Hirenkumar Patel, Alice A. Raad, Adelaide Revell, Michelle N. Rheault, Cynthia Silva, Rajasree Sreedharan, Tarak Srivastava, Julia Steinke, Susan Sumner, Katherine Twombley, Scott E. Wenderfer, Tetyana L. Vasylyeva, Chia-shi Wang, Donald J. Weaver, Craig S. Wong, Hong Yin, Anand Achanti, Salem Almaani, Isabelle Ayoub, Milos N. Budisavljevic, Maggie D’Angelo, Huma Fatima, Ronald J. Falk, Agnes B. Fogo, Keisha Gibson, Dorey A. Glenn, Susan L. Hogan, J. Charles Jennette, Bruce A. Julian, Jason M. Kidd, Louis‐Philippe Laurin, H. Davis Massey, Amy K. Mottl, Shannon L. Murphy, Patrick H. Nachman, Tibor Nádasdy, Jan Novák, Samir M. Parikh, Caroline J. Poulton, Thomas Brian Powell, Bryce B. Reeve, Matthew B. Renfrow, Monica L. Reynolds, Dana V. Rizk, Brad H. Rovin, Virginie Royal, Neil Sanghani, Sally Self, Sharon G. Adler, Nada Alachkar, Charles E. Alpers, Raed Bou Matar, Carmen Avila‐Casado, Serena M. Bagnasco, Emily Brede, Elizabeth Brown, Daniel Cattran, Michael Choi, Katherine M. Dell, Darren A. DeWalt, Michelle Denburg, Ram Dukkipati, Fernando C. Fervenza, Alessia Fornoni, Crystal A. Gadegbeku, Patrick Gipson, Anny Gonzalez-Zea, Leah Hasely, Elizabeth Hendren, Sangeeta Hingorani, Michelle Hladunewich, Jonathan Hogan, Lawrence B. Holzman, Jean Hou, J. Ashley Jefferson, Kenar D. Jhaveri, Duncan B. Johnstone, Frederick J. Kaskel, Amy Kogan, Jeffrey B. Kopp, Richard A. Lafayette, Kevin V. Lemley, Laura Málaga-Diéguez, Kevin Meyers, Alicia M. Neu, Michelle M. O’Shaughnessy, John F. O’Toole, Andrea L. Oliverio, Matthew Palmer, Rulan S. Parekh, Renée Pitter, Heather N. Reich, Kimberly Reidy, Helbert Rondon‐Berrios, Kamalanathan K. Sambandam, Matthew G. Sampson, John R. Sedor, David T. Selewski, Christine B. Sethna, Jeffrey R. Schelling, C. John Sperati, Agnieszka Swiatecka‐Urban, Howard Trachtman, Katherine R. Tuttle, Meryl Waldman, Joseph Weisstuch, Roger C. Wiggins, David Williams, Cheryl A. Winkler, Suzanne Vento, Eric W. Young, Olga Zhdanova, Laura Barisoni, Charlotte A. Beil, Richard Eikstadt, Brenda W. Gillespie, Debbie S. Gipson, John Graff, Stephen M. Hewitt, Peg Hill-Callahan, Margaret E. Helmuth, Emily Herreshoff, Matthias Kretzler, Chrysta Lienczewski, Sarah Mansfield, Laura Mariani, Keith McCullough, Nicholas Moore, Cynthia C. Nast, Bruce Robinson, Melissa Sexton, Jonathan P. Troost, Matthew Wladkowski, Jarcy Zee, Dawn Zinsser, Lisa M. Guay‐Woodford,

Dialysis and Renal Disease Management

There is scant literature describing the effect of glomerular disease on health-related quality of life (HRQOL). The Cure Glomerulonephropathy study (CureGN) is an international longitudinal cohort study of children and adults with four primary glomerular diseases (minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy). HRQOL is systematically assessed using items from the Patient-Reported Outcomes Measurement Informative System (PROMIS). We assessed the relationship between HRQOL and demographic and clinical variables in 478 children and 1115 adults at the time of enrollment into CureGN. Domains measured by PROMIS items included global assessments of health, mobility, anxiety, fatigue, and sleep impairment, as well as a derived composite measure incorporating all measured domains. Multivariable models were created that explained 7 to 32% of variance in HRQOL. Patient-reported edema consistently had the strongest and most robust association with each measured domain of HRQOL in multivariable analysis (adjusted β [95% CI] for composite PROMIS score in children, -5.2 [-7.1 to -3.4]; for composite PROMIS score in adults, -6.1 [-7.4 to -4.9]). Female sex, weight (particularly obesity), and estimated glomerular filtration rate were also associated with some, but not all, domains of HRQOL. Primary diagnosis, disease duration, and exposure to immunosuppression were not associated with HRQOL after adjustment. Sensitivity analyses and interaction testing demonstrated no significant association between disease duration or immunosuppression and any measured domain of HRQOL. Thus, patient-reported edema has a consistent negative association with HRQOL in patients with primary glomerular diseases, with substantially greater impact than other demographic and clinical variables. There is scant literature describing the effect of glomerular disease on health-related quality of life (HRQOL). The Cure Glomerulonephropathy study (CureGN) is an international longitudinal cohort study of children and adults with four primary glomerular diseases (minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy). HRQOL is systematically assessed using items from the Patient-Reported Outcomes Measurement Informative System (PROMIS). We assessed the relationship between HRQOL and demographic and clinical variables in 478 children and 1115 adults at the time of enrollment into CureGN. Domains measured by PROMIS items included global assessments of health, mobility, anxiety, fatigue, and sleep impairment, as well as a derived composite measure incorporating all measured domains. Multivariable models were created that explained 7 to 32% of variance in HRQOL. Patient-reported edema consistently had the strongest and most robust association with each measured domain of HRQOL in multivariable analysis (adjusted β [95% CI] for composite PROMIS score in children, -5.2 [-7.1 to -3.4]; for composite PROMIS score in adults, -6.1 [-7.4 to -4.9]). Female sex, weight (particularly obesity), and estimated glomerular filtration rate were also associated with some, but not all, domains of HRQOL. Primary diagnosis, disease duration, and exposure to immunosuppression were not associated with HRQOL after adjustment. Sensitivity analyses and interaction testing demonstrated no significant association between disease duration or immunosuppression and any measured domain of HRQOL. Thus, patient-reported edema has a consistent negative association with HRQOL in patients with primary glomerular diseases, with substantially greater impact than other demographic and clinical variables. The 4 major primary glomerular diseases—minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and IgA nephropathy (IgAN)—represent some of the most common causes of chronic kidney disease managed by nephrologists. These diseases are a significant cause of end-stage kidney disease across all ages in the United States, accounting for 6.6% of all cases and up to 13.1% of cases in children.1United States Renal Data System2016 USRDS annual data report: epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD2016Google Scholar The treatment of glomerular diseases is associated with complications including infections, thromboembolism, and acute kidney injury, and result in frequent hospitalizations and significant burden on the health care system.2Rheault M.N. Zhang L. Selewski D.T. et al.AKI in children hospitalized with nephrotic syndrome.Clin J Am Soc Nephrol. 2015; 10: 2110-2118Crossref PubMed Scopus (63) Google Scholar Although the medical burden of glomerular diseases is well known, little has been published about their impact on the quality of life of affected patients. Understanding the perspective of the patient can help optimize care, education, and anticipatory counseling provided by health care teams.3Selewski D.T. Thompson A. Kovacs S. et al.Patient-reported outcomes in glomerular disease.Clin J Am Soc Nephrol. 2017; 12: 140-148Crossref PubMed Scopus (23) Google Scholar Both the National Institutes of Health and the Food and Drug Administration have set forth an imperative to examine the full disease experience of patients and patient-reported outcomes (PROs) in medical decision making, research, and clinical trials.4Choudhry S. Bagga A. Hari P. et al.Efficacy and safety of tacrolimus versus cyclosporine in children with steroid-resistant nephrotic syndrome: a randomized controlled trial.Am J Kidney Dis. 2009; 53: 760-769Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar, 5Perrone R.D. Coons S.J. Cavanaugh K. et al.Patient-reported outcomes in clinical trials of CKD-related therapies: report of a symposium sponsored by the National Kidney Foundation and the U.S. Food and Drug Administration.Am J Kidney Dis. 2013; 62: 1046-1057Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar Although research has advanced the understanding of health-related quality of life (HRQOL) in conditions such as advanced kidney failure,6Da Silva-Gane M. Wellsted D. Greenshields H. et al.Quality of life and survival in patients with advanced kidney failure managed conservatively or by dialysis.Clin J Am Soc Nephrol. 2012; 7: 2002-2009Crossref PubMed Scopus (145) Google Scholar there is a paucity of data describing HRQOL in the primary glomerular diseases. Cross-sectional studies of children with nephrotic syndrome have included a description of HRQOL using instruments such as Patient-Reported Outcomes Measurement Information System (PROMIS) and PedsQL, finding substantial impairments in quality of life in areas such as social functioning and pain interference, with associations noted with disease duration and specific therapies.7Selewski D.T. Troost J.P. Massengill S.F. et al.The impact of disease duration on quality of life in children with nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study.Pediatr Nephrol. 2015; 30: 1467-1476Crossref PubMed Scopus (40) Google Scholar, 8Ruth E.M. Landolt M.A. Neuhaus T.J. et al.Health-related quality of life and psychosocial adjustment in steroid-sensitive nephrotic syndrome.J Pediatr. 2004; 145: 778-783Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar Quality-of-life impairments also have been shown in small studies of adults with nephrotic syndrome.9Gipson D.S. Trachtman H. Kaskel F.J. et al.Clinical trials treating focal segmental glomerulosclerosis should measure patient quality of life.Kidney Int. 2011; 79: 678-685Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar, 10Liborio A.B. Santos J.P. Minete N.F. et al.Proteinuria is associated with quality of life and depression in adults with primary glomerulopathy and preserved renal function.PLoS One. 2012; 7: e37763Crossref PubMed Scopus (19) Google Scholar, 11Shutto Y. Yamabe H. Shimada M. et al.Quality of life in patients with minimal change nephrotic syndrome.ScientificWorldJournal. 2013; 2013124315Crossref PubMed Scopus (7) Google Scholar Very little is known about HRQOL in patients with IgAN or MN, and scant effort has been made to comprehensively identify variables associated with HRQOL broadly in glomerular diseases. The Cure Glomerulonephropathy study (CureGN) is a multicenter longitudinal cohort study of children and adults with the 4 major primary glomerular diseases (MCD, FSGS, MN, and IgAN). The aims of the current study are to describe the HRQOL and to determine the variables associated with HRQOL at enrollment in the CureGN cohort across age and disease groups. A Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) flow diagram of included patients from CureGN is shown in Figure 1. There were 478 children and 1115 adults with HRQOL data available at enrollment. These cohorts are described in Tables 1 and 2, respectively. An additional 42 children and 18 adults did not have HRQOL data available, representing only 8% and 2% of the available pediatric and adult CureGN participants (Supplementary Tables S1 and S2). The distribution of diseases differed between the pediatric and adult cohorts. From the IgAN cohort, IgA vasculitis (IgAV, formerly known as Henoch-Schönlein purpura) was analyzed separately. The proportion of children with MCD was greater than adults (28% vs. 13%, respectively), as was the proportion of children with IgAV (16% vs. 5%). The proportions of children and adults with FSGS (24% vs. 24%) and IgAN (26% vs. 31%) were similar. There were fewer females than males in both the pediatric and adult cohorts. Racial and ethnic distributions were similar for children and adults, two thirds of participants were white and nearly 90% were of non-Hispanic ethnicity. There were substantial differences in racial distribution among the diagnoses, with black participants more likely to have FSGS and less likely to have IgAN or IgAV. Thirty percent of children and 37% of adults were classified as obese.Table 1Description of pediatric CureGN patients with PROMIS data at enrollmentVariablesAllMCDFSGSMNIgANIgAVN (%)478 (100)134 (28)115 (24)28 (6)126 (26)75 (16)Median age, yr (IQR)13 (10–15)12 (9–14)14 (12–16)15 (13–16)14 (11–16)12 (9–14)Female, n (%)202 (42)58 (43)55 (48)16 (57)48 (38)25 (33)Race, n (%) Black/African American92 (19)35 (26)43 (37)8 (29)4 (3)2 (3) White/Caucasian319 (67)77 (57)59 (51)15 (54)103 (82)65 (87) Other67 (14)22 (16)13 (11)5 (18)19 (15)8 (11) Hispanic, n (%)49 (10)12 (9)12 (10)6 (21)14 (11)5 (7)Obese, n (%)142 (30)33 (25)42 (37)13 (46)29 (23)25 (33)Hematuria, n (%)137 (29)13 (10)6 (5)2 (7)89 (71)27 (36)Any edema, n (%)152 (32)54 (40)40 (35)17 (61)22 (17)19 (25)Median UP:C (IQR)0.5 (0.1–2.2)0.4 (0.1–2.7)1.2 (0.2–2.8)3.2 (0.9–7.4)0.3 (0.1–0.8)0.5 (0.2–1.4) 3.5, n (%)76 (16)24 (18)20 (17)13 (46)9 (7)10 (13) Missing, n (%)48 (10)15 (11)18 (16)2 (7)9 (7)4 (5)Median eGFR (IQR)97 (82–116)111 (93–127)90 (60–108)97 (87–114)94 (81–109)101 (90–121) 90, n (%)294 (62)98 (73)55 (48)18 (64)69 (55)54 (72) Missing, n (%)25 (5)10 (7)6 (5)1 (4)6 (5)2 (3)IST within 60 days, n (%) None345 (72)90 (67)81 (70)16 (57)107 (85)51 (68) Corticosteroids alone75 (16)22 (16)16 (14)5 (18)16 (13)16 (21) Other IST58 (12)22 (16)18 (16)7 (25)3 (2)8 (11)Past 60 days median prednisone dose, mg/kg/d (IQR)0.2 (0.1–0.5)0.2 (0.1–0.5)0.1 (0.1–0.3)0.2 (0.1–0.5)0.4 (0.1–0.7)0.3 (0.2–0.5)IST type, n (%) Corticosteroids105 (22)31 (23)25 (22)10 (36)17 (13)22 (29) CNI35 (7)15 (11)11 (10)7 (25)1 (1)1 (1) Cyclophosphamide1 (0)0 (0)0 (0)0 (0)0 (0)1 (1) Mycophenolate19 (4)5 (4)6 (5)0 (0)2 (2)6 (8) Rituximab8 (2)4 (3)4 (3)0 (0)0 (0)0 (0)Median disease duration, mo (IQR)18 (5–42)34 (13–61)18 (6–45)6 (1–17)15 (4–34)9 (3–20)CNI, calcineurin inhibitor; eGFR, estimated glomerular filtration rate; FSGS, focal segmental glomerulosclerosis; IgAN, IgA nephropathy; IgAV, IgA vasculitis; IQR, interquartile range; IST, immunosuppressive therapy; MCD, minimal change disease; MN, membranous nephropathy; UP:C, urinary protein:creatinine ratio. Open table in a new tab Table 2Description of adult CureGN patients with PROMIS data at enrollmentVariablesAllMCDFSGSMNIgANIgAVN (%)1115 (100)141 (13)271 (24)305 (27)344 (31)54 (5)Median age, yr (IQR)44 (31–58)43 (26–58)42 (29–56)55 (43–65)40 (30–51)35 (25–48)Female, n (%)482 (43)77 (55)134 (49)110 (36)140 (41)21 (39)Race, n (%) Black/African American165 (15)21 (15)81 (30)45 (15)17 (5)1 (2) White/Caucasian747 (67)95 (67)144 (53)218 (71)245 (71)45 (83) Other203 (18)25 (18)46 (17)42 (14)82 (24)8 (15) Hispanic, n (%)153 (14)11 (8)47 (17)27 (9)61 (18)7 (13)Obese, n (%)415 (37)52 (37)109 (40)115 (38)113 (33)26 (48)Hematuria, n (%)131 (12)3 (2)8 (3)10 (3)98 (28)12 (22)Any edema, n (%)643 (58)91 (65)175 (65)212 (70)139 (40)26 (48)Median UP:C (IQR)1.9 (0.6–4.4)1.8 (0.1–6.8)2.6 (0.9–4.9)3.3 (1.1–5.9)1.0 (0.4–2.2)1.0 (0.3–1.9) 3.5, n (%)329 (30)51 (36)90 (33)137 (45)43 (13)8 (15) Missing, n (%)86 (8)15 (11)19 (7)23 (8)27 (8)2 (4)Median eGFR (IQR)68 (41–96)93 (63–114)57 (34–86)72 (46–94)57 (38–88)84 (51–112) 90, n (%)323 (29)70 (50)60 (22)86 (28)83 (24)24 (44) Missing, n (%)21 (2)4 (3)4 (1)6 (2)6 (2)1 (2)IST within 60 days, n (%) None860 (77)81 (57)204 (75)247 (81)296 (86)32 (59) Corticosteroids alone119 (11)27 (19)28 (10)17 (6)31 (9)16 (30) Other IST136 (12)33 (23)39 (14)41 (13)17 (5)6 (11)Past 60 days median prednisone dose, mg/kg/d (IQR)0.1 (0.1–0.3)0.2 (0.1–0.5)0.1 (0.1–0.5)0.1 (0.1–0.1)0.1 (0.1–0.3)0.2 (0.1–0.3)IST type, n (%) Corticosteroids160 (14)35 (25)39 (14)31 (10)35 (10)20 (37) CNI79 (7)21 (15)28 (10)25 (8)5 (1)0 (0) Cyclophosphamide14 (1)2 (1)0 (0)11 (4)0 (0)1 (2) Mycophenolate31 (3)7 (5)8 (3)0 (0)12 (3)4 (7) ACTH3 (0)2 (1)1 (0)0 (0)0 (0) Rituximab13 (1)4 (3)3 (1)5 (2)0 (0)1 (2)Median disease duration, mo (IQR)16 (5–40)20 (7–41)21 (6–45)14 (5–36)15 (4–41)10 (2–25)ACTH, adrenocorticotropic hormone gel; CNI, calcineurin inhibitor; eGFR, estimated glomerular filtration rate; FSGS, focal segmental glomerulosclerosis; IgAN, IgA nephropathy; IgAV, IgA vasculitis; IQR, interquartile range; IST, immunosuppressive therapy; MCD, minimal change disease; MN, membranous nephropathy; UP:C, urinary protein:creatinine ratio. Open table in a new tab CNI, calcineurin inhibitor; eGFR, estimated glomerular filtration rate; FSGS, focal segmental glomerulosclerosis; IgAN, IgA nephropathy; IgAV, IgA vasculitis; IQR, interquartile range; IST, immunosuppressive therapy; MCD, minimal change disease; MN, membranous nephropathy; UP:C, urinary protein:creatinine ratio. ACTH, adrenocorticotropic hormone gel; CNI, calcineurin inhibitor; eGFR, estimated glomerular filtration rate; FSGS, focal segmental glomerulosclerosis; IgAN, IgA nephropathy; IgAV, IgA vasculitis; IQR, interquartile range; IST, immunosuppressive therapy; MCD, minimal change disease; MN, membranous nephropathy; UP:C, urinary protein:creatinine ratio. Only 32% of children reported any edema at presentation, as opposed to 58% of adults. Among both children and adults, edema was less common in IgAN or IgAV. The median urine protein:creatinine ratio (UP:C) was 0.5 (interquartile range [IQR], 0.1–2.2) for the pediatric cohort and 1.9 (IQR, 0.6–4.4) for the adult cohort. Thirty-six percent of the pediatric cohort, but only 16% of the adult cohort, had a UP:C less than 0.3, indicating relatively more pediatric participants were in complete disease remission at the time of assessment. Accordingly, the median estimated glomerular filtration rate (eGFR) was 97 ml/min per 1.73 m2 (IQR, 82–116 ml/min per 1.73 m2) for children but 68 ml/min per 1.73 m2 (IQR, 41–96 ml/min per 1.73 m2) for adults, and 91% of children with available data had an eGFR greater than 60 ml/min per 1.73 m2, while in adults this proportion was 56%. A minority of both children and adults had been exposed to immunosuppressive therapy (IST) within 60 days before enrollment (28% and 23%, respectively). Among those recently exposed to IST, corticosteroids were the most common agent used in both cohorts and among all diseases. Baseline HRQOL measures are summarized in Figure 2, which shows the distribution of scores across the 4 PROMIS domains measured in children and the 5 PROMIS domains measured in adults, as well as the calculated composite scores. Means and SDs are reported in the figures. The shapes of the distributions reflect the number of questionnaire items used for each domain. For example, anxiety and sleep impairment were each measured by a single 5-item Likert scale, thus those distributions have 5 discrete peaks and resulted in skewed values.Figure 2Distribution of PROMIS domains in (a) children and (b) adults. Note that the direction of better versus worse scores differs among domains and is indicated by arrows for each panel. HRQOL, health-related quality of life; PROMIS, Patient-Reported Outcomes Measurement Information System.View Large Image Figure ViewerDownload Hi-res image Download (PPT) To identify potential predictors of HRQOL, multivariable linear regression models were created for each PROMIS domain. Initial analyses showed that the presence of any edema was associated strongly with worse HRQOL across both children and adults for every PROMIS domain. Using negative numbers to indicate worse HRQOL, adjusted linear regression coefficients (β) for the pediatric domains were as follows: –3.6 (95% confidence interval [CI], –5.4 to –1.8) for global health, –4.4 (95% CI, –6.1 to –2.7) for mobility, –6.4 (95% CI, –8.6 to –4.2) for fatigue, –2.1 (95% CI, –3.4 to –0.9) for anxiety, and –5.2 (95% CI, –7.1 to –3.4) for the composite score; and adult domains were as follows: –6.8 (95% CI, –8.0 to –5.6) for global physical health, –3.9 (95% CI, –5.0 to –2.8) for global mental health, –5.8 (95% CI, –7.0 to –4.5) for fatigue, –4.8 (95% CI, –5.8 to –3.8) for sleep impairment, –2.9 (95% CI, –3.9 to –1.9) for anxiety, and –6.1 (95% CI, –7.4 to –4.9) for the composite score (Figure 3). Because of the strength of this association, edema was characterized further by combining aspects of location and severity to create ordinal variables, and these variables were entered into multivariable models. The worst reported edema severity for each diagnostic group in children and adults is shown in Figure 4. Compared with children, adults reported more severe edema scores and were less likely to report no edema, even within diseases. The full distribution of edema scores by diagnosis and age group is available in Supplementary Tables S3 and S4.Figure 4Worst edema severity by diagnosis in (a) children and (b) adults. FSGS, focal segmental glomerulosclerosis; IgAN, IgA nephropathy; IgAV, IgA vasculitis; MCD, minimal change disease; MN, membranous nephropathy.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The results of the final multivariable analyses are summarized in Tables 3 and 4 (unadjusted univariable analyses are shown in the Supplementary Tables S5–S15). In the final models, worst edema remained robustly associated with every HRQOL domain in adults: using negative numbers to indicate worse HRQOL, linear coefficients β were as follows: –1.6 (95% CI, –2.2 to –1.1) for global physical health, –0.7 (95% CI, –1.3 to –0.1) for global mental health, –0.6 (95% CI, –0.3 to –1.0) for anxiety, –2.1 (95% CI, –1.7 to –2.5) for fatigue, –1.1 (95% CI, –0.7 to –1.4) for sleep impairment, and –1.6 (95% CI, –2.0 to –1.2) for the composite score. Various edema variables were those most associated with HRQOL domains in children as well (Table 3). For certain domains, specific locations of edema (e.g., face, leg, genitals) had a residual association beyond worst edema, although the majority of the variance explained in most models was from worst edema. Increasing severity of edema was associated with stepwise worsening HRQOL in most domains for both children and adults (Figure 5), and η2 values were improved (indicating greater variance explained) by using the ordinal worst edema instead of the binary any edema. Despite the use of various edema terms, none of the final multivariable models showed evidence of significant multicollinearity (as indicated by the variance inflation factors in Tables 3 and 4, in which a variance inflation factor > 4 indicates potential collinearity and a variance inflation factor > 10 indicates multicollinearity requiring correction).Table 3Final pediatric multivariable models for predicting HRQOL across measured domainsβ (95% CI)PModel η2Type I η2Type III η2VIFGlobal assessment of health0.09 Worst edema–1.5 (–2.1 to –0.9)<0.0010.060.061.06Weight<0.0010.030.03 Underweight–4.6 (–10.5 to 1.3)0.131.02 Normal weightRefRefRef Overweight–0.7 (–3.0 to 1.6)0.541.18 Obese–3.8 (–5.7 to –1.9)<0.0011.15Anxiety0.07 Total edema0.3 (0.2–0.4)<0.0010.060.061.01 Sex (female vs. male)1.4 (0.2–2.6)0.020.010.011.01Fatigue0.17 Face edema5.8 (3.2–8.4)<0.0010.090.031.24 Hand edema7.9 (4.2–11.7)<0.0010.040.031.27 Sex (female vs. male)3.1 (1.1–5.1)0.0020.020.021.03Weight0.010.020.02 Underweight–6.3 (–13.5 to 0.9)0.091.03 Normal weightRefRef Overweight1.0 (–1.7 to 3.8)0.471.23 Obese2.9 (0.6–5.2)0.011.15Mobility0.15 Whole-body edema–4.9 (–8.6 to –1.2)0.010.090.012.10 Arm edema–4.6 (–9.0 to –0.2)0.040.020.012.10 Leg edema–3.7 (–6.1 to –1.4)0.0020.020.021.37Weight0.020.020.02 Underweight–1.5 (–7.3 to 4.2)0.601.02 Normal weightRefRefRef Overweight–0.5 (–2.6 to 1.6)0.651.17 Obese–2.8 (–4.6 to –1.0)0.0021.17Composite0.21 Worst edema–1.9 (–2.6 to –1.2)<0.0010.150.051.46 Arm edema–6.9 (–11.2 to –2.6)0.0020.020.021.45 Sex (female vs. male)–2.5 (–4.2 to –0.8)0.0030.010.021.03Weight0.0010.030.03 Underweight0.8 (–5.6 to 7.1)0.811.02 Normal weightRefRefRef Overweight–0.7 (–3.0 to 1.6)0.551.21 Obese–3.8 (–5.7 to –1.8)0.0011.15For each domain, a higher score means more of that item (e.g., higher anxiety scores imply worse anxiety, higher mobility scores imply better mobility). For the composite score, higher is better. Model η2 = overall η2 for the adjusted multivariable model; type I η2 = model η2 in an unadjusted model of the variable by itself (i.e., the various type I η2 values will sum to the model η2); type III η2 = the change in the total model η2 after removing that variable from the model.CI, confidence interval; HRQOL, health-related quality of life; VIF, variance inflation factor. Open table in a new tab Table 4Final adult multivariable models for predicting HRQOL across measured domainsβ (95% CI)PModel η2Type I η2Type III η2VIFGlobal assessment of physical health0.32 Worst edema–1.6 (–2.2 to –1.1)<0.0010.260.023.52 Total edema–0.3 (–0.4 to –0.2)<0.0010.010.023.48 eGFR (per 30-unit change)1.1 (0.7–1.6)<0.0010.020.021.02 Sex (female vs. male)–1.6 (–2.6 to –0.5)0.0020.010.011.02Weight<0.0010.020.02 Underweight–2.0 (–7.0 to 2.9)0.431.02 Normal weightRefRefRef Overweight–1.1 (–2.4 to 0.1)0.081.04 Obese–3.1 (–4.3 to –1.9)0.021.01Global assessment of mental health0.15 Worst edema–0.7 (–1.3 to –0.1)0.020.120.013.48 Total edema–0.3 (–0.5 to –0.2)<0.0010.020.023.47 eGFR (per 30-unit change)0.8 (0.3–1.3)<0.0010.010.011.01Anxiety0.12 Worst edema0.6 (0.3–1.0)0.0010.070.011.74 Hand edema2.1 (0.9–3.5)0.0010.010.011.57 Genital edema2.2 (0.3–4.1)0.020.010.011.28 ln(UP:C) (per doubling)0.4 (0.1–0.7)0.010.010.011.12 Hematuria (yes vs. no)2.5 (1.0–4.0)0.0010.010.011.04 Sex (female vs. male)2.1 (1.1–3.0)<0.0010.010.021.04Fatigue0.23 Worst edema2.1 (1.7–2.5)<0.0010.200.081.49 Hand edema3.6 (2.1–5.1)<0.0010.020.021.49 eGFR (per 30-unit change)–0.5 (–1.0 to –0.1)0.04<0.01<0.011.01 Sex (female vs. male)2.2 (1.1–3.3)<0.0010.010.011.03Sleep impairments0.15 Worst edema1.1 (0.7–1.4)<0.0010.110.031.61 Hand edema3.1 (1.7–4.4)<0.0010.020.021.52 Genital edema2.4 (0.6–4.3)0.010.010.011.27 eGFR (per 30-unit change)–0.6 (–1.1 to –0.2)0.009<0.010.011.23 Age (per 10-unit change)–0.6 (–0.9 to –0.3)<0.0010.010.011.24Composite0.22 Worst edema–1.6 (–2.0 to –1.2)<0.0010.170.041.62 Hand edema–3.8 (–5.3 to –2.3)<0.0010.030.021.55 Genital edema–3.4 (–5.5 to –1.2)<0.0010.010.011.28 Hematuria (yes vs. no)–2.5 (–4.1 to –0.8)0.003<0.010.011.03 Sex (female vs. male)–2.2 (–3.2 to –1.1) 40 mg/d prednisone equivalent in adults and >1 mg/kg/d in children) as well as the average daily corticosteroid dose in the prior 60 day