Citations 2
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.
TGF-β1 is an Autocrine Mediator of Renal Tubular Epithelial Cell Growth and Collagen IV Production
Grande, Joseph P. , Warner, Gina M., Walker, Henry J. , Yusufi, Ahad Noor Khan , Gray, Catherine , Nath, Karl A. , Cheng, Jingfei , Kopp, Jeffrey B.
Experimental Biology and Medicine | January 8, 2018 | Volume: 227 | Issue: 3 | Pages: 171-181
Recent studies in cultured cells have provided evidence that a variety of pathobiologic stimuli, including high glucose, angiotensin II, and thromboxane A 2 , trigger a signaling pathway leading to autocrine induction of TGF-β1. TGF-β1 production through this pathway may profoundly affect cell growth, matrix synthesis, and response to injury. This study examines the role of autocrine versus exogenously added TGF-β1 in cellular proliferation and collagen IV production, critical targets of TGF-β1 signaling, using renal cells derived from TGF-β1 knockout (KO) animals or wild-type (WT) controls. Growth of WT and KO cells was assessed by cell counting and [ 3 H]thymidine uptake. Basal and TGF-β1-stimulated collagen production was assessed by Northern and Western blotting; transcriptional activity of the α1(IV) collagen gene was assessed by transient transfection analysis. KO cells grew at a faster rate than WT cells carefully matched for plating density and passage number. This increased growth rate was paralleled by increases in [ 3 H]thymidine uptake. KO cells expressed lower levels of the cell cycle inhibitors p21 and p27 than WT cells. KO cells failed to express TGF-β1, as expected. Basal TGF-β3 mRNA levels were higher in KO cells than in WT cells. WT cells expressed higher basal levels of TGF-β2 mRNA than KO cells. Basal α1(IV) and α2(IV) collagen mRNA and protein expression were significantly lower in KO cells than WT cells. Administration of exogenous TGF-β1 induced collagen IV production in both KO and WT cells. Although basal transcriptional activity of an α1(IV) collagen-CAT construct was lower in KO cells than WT cells, administration of exogenous TGF-β1 was associated with significant increases in transcriptional activity of this construct in both KO and WT cells. These studies provide evidence that autocrine production of TGF-β1 may play a critical role in regulation of growth and basal collagen IV production by renal tubular epithelial cells.