Browsing by Author "Khalid, Myda"

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    Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome: The ATLANTIS Randomized Trial
    (American Society of Nephrology, 2018-12-07) Wang, Chia-shi; Travers, Curtis; McCracken, Courtney; Leong, Traci; Gbadegesin, Rasheed; Quiroga, Alejandro; Benfield, Mark R.; Hidalgo, Guillermo; Srivastava, Tarak; Lo, Megan; Yadin, Ora; Mathias, Robert; Araya, Carlos E.; Khalid, Myda; Orjuela, Alvaro; Zaritsky, Joshua; Al-Akash, Samhar; Kamel, Margret; Greenbaum, Larry A.; Pediatrics, School of Medicine
    Background and objectives There is renewed interest in adrenocorticotropic hormone (ACTH) for the treatment of nephrotic syndrome. We evaluated the efficacy and safety of ACTH in children with frequently relapsing or steroid-dependent nephrotic syndrome in a randomized trial. Design, setting, participants, & measurements Participants aged 2–20 years old with frequently relapsing or steroid-dependent nephrotic syndrome were enrolled from 16 sites in the United States and randomized 1:1 to ACTH (repository corticotropin injection) or no relapse-preventing treatment. ACTH treatment regimen was 80 U/1.73 m2 administered twice weekly for 6 months, followed by 40 U/1.73 m2 administered twice weekly for 6 months. The primary outcome was disease relapse during the first 6 months. Participants in the control group were offered crossover to ACTH treatment if they relapsed within 6 months. Secondary outcomes were relapse after ACTH dose reduction and treatment side effects. Results The trial was stopped at a preplanned interim analysis after enrollment of 31 participants because of a lack of discernible treatment efficacy. Fourteen out of 15 (93%) participants in the ACTH arm experienced disease relapse in the first 6 months, with a median time to first relapse of 23 days (interquartile range, 9–32), compared with 15 out of 16 (94%) participants and at a median of 21 days (interquartile range, 14–51) in the control group. There was no difference in the proportion of relapsed patients (odds ratio, 0.93; 95% confidence interval, 0.05 to 16.40; P>0.99) or time to first relapse (hazard ratio, 1.03; 95% confidence interval, 0.50 to 2.15; P=0.93). Thirteen out of 16 participants in the control group crossed over to ACTH treatment. Three out of 28 participants completed 12 months of ACTH treatment; the others exited the trial because of frequent relapses or side effects. There were no disease relapses after ACTH dose reduction among the three participants. Most side effects were mild and similar to side effects of corticosteroids. Conclusions ACTH at 80 U/1.73 m2 administered twice weekly was ineffective at preventing disease relapses in pediatric nephrotic syndrome.
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    Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study
    (Elsevier, 2018-08-03) Selewski, David T.; Ambruzs, Josephine M.; Appel, Gerald B.; Bomback, Andrew S.; Matar, Raed Bou; Cai, Yi; Cattran, Daniel C.; Chishti, Aftab S.; D’Agati, Vivette D.; D’Alessandri-Silva, Cynthia J.; Gbadegesin, Rasheed A.; Hogan, Jonathan J.; Iragorri, Sandra; Jennette, J. Charles; Julian, Bruce A.; Khalid, Myda; Lafayette, Richard A.; Liapis, Helen; Lugani, Francesca; Mansfield, Sarah A.; Mason, Sherene; Nachman, Patrick H.; Nast, Cynthia C.; Nester, Carla M.; Noone, Damien G.; Novak, Jan; O’Shaughnessy, Michelle M.; Reich, Heather N.; Rheault, Michelle N.; Rizk, Dana V.; Saha, Manish K.; Sanghani, Neil S.; Sperati, C. John; Sreedharan, Rajasree; Srivastava, Tarak; Swiatecka-Urban, Agnieszka; Twombley, Katherine; Vasylyeva, Tetyana L.; Weaver, Donald J.; Yin, Hong; Zee, Jarcy; Falk, Ronald J.; Gharavi, Ali G.; Gillespie, Brenda W.; Gipson, Debbie S.; Greenbaum, Larry A.; Holzman, Lawrence B.; Kretzler, Matthias; Robinson, Bruce M.; Smoyer, William E.; Flessner, Michael; Guay-Woodford, Lisa M.; Kiryluk, Krzysztof; CureGN Consortium; Pediatrics, School of Medicine
    Introduction: The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients. Methods: Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment. Results: A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001). Conclusion: This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies.
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    Farm animal contact is associated with progression to Hemolytic uremic syndrome in patients with Shiga toxin-producing Escherichia coli — Indiana, 2012–2018
    (Elsevier, 2020-12) Vachon, Madhura S.; Khalid, Myda; Tarr, Gillian A. M.; Hedberg, Craig; Brown, Jennifer A.; Pediatrics, School of Medicine
    Background: Hemolytic uremic syndrome (HUS) is a life-threatening complication of Shiga toxin-producing Escherichia coli (STEC) infection. The relationship between STEC exposure and severity of clinical outcomes is not well documented. We examined whether direct contact with farm animals increased the likelihood of HUS among Indiana residents diagnosed with STEC. Methods: Exposure data for laboratory-confirmed STEC cases among Indiana residents during 2012-2018 were retrieved. Logistic regression and mediation analysis were performed to determine the extent to which a history of direct contact with farm animals was associated with post-diarrheal HUS independent of age and mediated by stx2 gene presence. Results: A total of 784 STEC cases were retrieved. Of these, 46 (6%) developed HUS. Complete exposure data were available for 600 (77%) cases. A total of 24 (52%) HUS patients reported direct contact with farm animals, while 114 (21%) STEC patients who did not develop HUS reported this exposure. Among all STEC cases, HUS was associated with direct farm animal contact after adjusting for age (OR = 3.40, 95% CI: 1.81, 6.40). Detection of stx2 genes mediated 12% of the association between farm animal contact and HUS. Conclusions: Direct farm animal contact was a risk factor for development of HUS among laboratory-confirmed STEC cases, independent of stx2 presence. Direct farm animal contact should be considered a potential predictor of progression to HUS when patients present for care and the mechanism for its effect on virulence investigated.
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    Implementation of a Renal Precision Medicine Program: Clinician Attitudes and Acceptance
    (MDPI, 2020-03-26) Spiech, Katherine M.; Tripathy, Purnima R.; Woodcock, Alex M.; Sheth, Nehal A.; Collins, Kimberly S.; Kannegolla, Karthik; Sinha, Arjun D.; Sharfuddin, Asif A.; Pratt, Victoria M.; Khalid, Myda; Hains, David S.; Moe, Sharon M.; Skaar, Todd C.; Moorthi, Ranjani N.; Eadon, Michael T.; Medicine, School of Medicine
    A precision health initiative was implemented across a multi-hospital health system, wherein a panel of genetic variants was tested and utilized in the clinical care of chronic kidney disease (CKD) patients. Pharmacogenomic predictors of antihypertensive response and genomic predictors of CKD were provided to clinicians caring for nephrology patients. To assess clinician knowledge, attitudes, and willingness to act on genetic testing results, a Likert-scale survey was sent to and self-administered by these nephrology providers (N = 76). Most respondents agreed that utilizing pharmacogenomic-guided antihypertensive prescribing is valuable (4.0 ± 0.7 on a scale of 1 to 5, where 5 indicates strong agreement). However, the respondents also expressed reluctance to use genetic testing for CKD risk stratification due to a perceived lack of supporting evidence (3.2 ± 0.9). Exploratory sub-group analyses associated this reluctance with negative responses to both knowledge and attitude discipline questions, thus suggesting reduced exposure to and comfort with genetic information. Given the evolving nature of genomic implementation in clinical care, further education is warranted to help overcome these perception barriers.
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    Racial and Ethnic Disparities in Acute Care Utilization Among Patients With Glomerular Disease
    (Elsevier, 2023) Krissberg, Jill R.; O’Shaughnessy, Michelle M.; Smith, Abigail R.; Helmuth, Margaret E.; Almaani, Salem; Aviles, Diego H.; Brathwaite, Kaye E.; Cai, Yi; Cattran, Daniel; Gbadegesin, Rasheed; Glenn, Dorey A.; Greenbaum, Larry A.; Iragorri, Sandra; Jain, Koyal; Khalid, Myda; Kidd, Jason; Kopp, Jeffrey; Lafayette, Richard; Lane, Jerome C.; Lugani, Francesca; Nestor, Jordan G.; Parekh, Rulan S.; Reidy, Kimberly; Selewski, David T.; Sethna, Christine B.; Sperati, C. John; Tuttle, Katherine; Twombley, Katherine; Vasylyeva, Tetyana L.; Weaver, Donald J., Jr.; Wenderfer, Scott E.; Gibson, Keisha; CureGN Consortium; Pediatrics, School of Medicine
    Rationale & objective: The effects of race, ethnicity, socioeconomic status (SES), and disease severity on acute care utilization in patients with glomerular disease are unknown. Study design: Prospective cohort study. Setting & participants: 1,456 adults and 768 children with biopsy-proven glomerular disease enrolled in the Cure Glomerulonephropathy (CureGN) cohort. Exposure: Race and ethnicity as a participant-reported social factor. Outcome: Acute care utilization defined as hospitalizations or emergency department visits. Analytical approach: Multivariable recurrent event proportional rate models were used to estimate associations between race and ethnicity and acute care utilization. Results: Black or Hispanic participants had lower SES and more severe glomerular disease than White or Asian participants. Acute care utilization rates were 45.6, 29.5, 25.8, and 19.2 per 100 person-years in Black, Hispanic, White, and Asian adults, respectively, and 55.8, 42.5, 40.8, and 13.0, respectively, for children. Compared with the White race (reference group), Black race was significantly associated with acute care utilization in adults (rate ratio [RR], 1.76 [95% CI, 1.37-2.27]), although this finding was attenuated after multivariable adjustment (RR, 1.31 [95% CI, 1.03-1.68]). Black race was not significantly associated with acute care utilization in children; Asian race was significantly associated with lower acute care utilization in children (RR, 0.32 [95% CI 0.14-0.70]); no significant associations between Hispanic ethnicity and acute care utilization were identified. Limitations: We used proxies for SES and lacked direct information on income, household unemployment, or disability. Conclusions: Significant differences in acute care utilization rates were observed across racial and ethnic groups in persons with prevalent glomerular disease, although many of these difference were explained by differences in SES and disease severity. Measures to combat socioeconomic disadvantage in Black patients and to more effectively prevent and treat glomerular disease are needed to reduce disparities in acute care utilization, improve patient wellbeing, and reduce health care costs.
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    Racial-Ethnic Differences in Health-Related Quality of Life among Adults and Children with Glomerular Disease
    (Karger, 2021) Krissberg, Jill R.; Helmuth, Margaret E.; Almaani, Salem; Cai, Yi; Cattran, Daniel; Chatterjee, Debanjana; Gbadegesin, Rasheed A.; Gibson, Keisha L.; Glenn, Dorey A.; Greenbaum, Laurence A.; Iragorri, Sandra; Jain, Koyal; Khalid, Myda; Kidd, Jason M.; Kopp, Jeffrey B.; Lafayette, Richard; Nestor, Jordan G.; Parekh, Rulan S.; Reidy, Kimberly J.; Selewski, David T.; Sperati, C. John; Tuttle, Katherine R.; Twombley, Katherine; Vasylyeva, Tetyana L.; Weaver, Donald Jack; Wenderfer, Scott E.; O’Shaughnessy, Michelle M.; Pediatrics, School of Medicine
    Introduction: Disparities in health-related quality of life (HRQOL) have been inadequately studied in patients with glomerular disease. The aim of this study was to identify relationships between race/ethnicity, socioeconomic status, disease severity, and HRQOL in an ethnically and racially diverse cohort of patients with glomerular disease. Methods: Cure Glomerulonephropathy (CureGN) is a multinational cohort study of patients with biopsy-proven glomerular disease. Associations between race/ethnicity and HRQOL were determined by the following: 1. Missed school or work due to kidney disease; 2. Responses to Patient Reported Outcomes Measurement Information System (PROMIS) questionnaires. We adjusted for demographics, socioeconomic status, and disease characteristics using multivariable logistic and linear regression. Results: Black and Hispanic participants had worse socioeconomic status and more severe glomerular disease than White or Asian participants. Black adults missed work or school most frequently due to kidney disease (30% versus 16-23% in the other three groups, p=0.04), and had the worst self-reported global physical health (median score 44.1 versus 48.0-48.2, p<0.001) and fatigue (53.8 versus 48.5-51.1, p=0.002), compared to other racial/ethnic groups. However, these findings were not statistically significant with adjustment for socioeconomic status and disease severity, both of which were strongly associated with HRQOL in adults. Among children, disease severity but not race/ethnicity or socioeconomic status were associated with HRQOL. Conclusions: Among patients with glomerular disease enrolled in CureGN, the worse HRQOL reported by Black adults was attributable to lower socioeconomic status and more severe glomerular disease. No racial/ethnic differences in HRQOL were observed in children.
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    Treatment Patterns Among Adults and Children With Membranous Nephropathy in the Cure Glomerulonephropathy Network (CureGN)
    (Elsevier, 2019-12) O’Shaughnessy, Michelle M.; Troost, Jonathan P.; Bomback, Andrew S.; Hladunewich, Michelle A.; Ashoor, Isa F.; Gibson, Keisha L.; Matar, Raed Bou; Selewski, David T.; Srivastava, Tarak; Rheault, Michelle N.; Al-Uzri, Amira; Kogon, Amy J.; Khalid, Myda; Vento, Suzanne; Sanghani, Neil S.; Gillespie, Brenda W.; Gipson, Debbie S.; Wang, Chia-shi; Parsa, Afshin; Guay-Woodford, Lisa; Laurin, Louis-Philippe; Pediatrics, School of Medicine
    Introduction The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for Glomerulonephritis recommend that patients with membranous nephropathy (MN) at risk for progression receive immunosuppressive therapy (IST), usually after 6 months of observation. A cyclophosphamide (CYC) or calcineurin inhibitor (CNI)–based regimen is recommended as first-line IST. However, the extent to which KDIGO recommendations are adopted in practice remains largely unknown. Methods We evaluated prescribing practice among patients with primary MN (diagnosed 2010–2018) enrolled in the Cure Glomerulonephropathy Network (CureGN) cohort study. We also evaluated the availability of testing for phospholipase A2 receptor (PLA2R) in the contemporary era. Results Among 361 patients (324 adults and 37 children) with MN who were IST-naïve at biopsy and had at least 6 months of follow-up, 55% of adults and 58% of children initiated IST <6 months after biopsy. Of these, 1 in 5 had no indication for (i.e., urine protein-to-creatinine ratio [uPCR] <4 g/g) or an apparent contraindication to (i.e., an estimated glomerular filtration rate [eGFR] <30 ml/min per 1.73 m2) IST. As first-line IST, half of treated patients received either CYC (16% of adults; 0% of children) or a CNI (40% and 46%, respectively), whereas 1 in 5 received corticosteroid monotherapy (20% and 27%, respectively) and 1 in 6 rituximab (15% and 15%, respectively). More than 80% of surveyed centers had access to PLA2R testing. Conclusion These findings suggest that providers are not aware of, or lack confidence in, current KDIGO guidelines for MN. Treatment patterns observed in this cohort might critically inform the drafting of planned updates to KDIGO guidelines.