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207 results on '"Parikh, Chirag R"'

3. Associations of Baseline and Longitudinal Serum Uromodulin With Kidney Failure and Mortality: Results From the African American Study of Kidney Disease and Hypertension (AASK) Trial

Author

Chen, Teresa K., Estrella, Michelle M., Appel, Lawrence J., Surapaneni, Aditya L., Köttgen, Anna, Obeid, Wassim, Parikh, Chirag R., and Grams, Morgan E.

Abstract

Uromodulin (UMOD) is the most abundant protein found in urine and has emerged as a promising biomarker of tubule health. Circulating UMOD is also detectable, but at lower levels. We evaluated whether serum UMOD levels were associated with the risks of incident kidney failure with replacement therapy (KFRT) and mortality.

Published
2024
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4. The ASSESS-AKI Study found urinary epidermal growth factor is associated with reduced risk of major adverse kidney events

Author

Menez, Steven, Wen, Yumeng, Xu, Leyuan, Moledina, Dennis G., Thiessen-Philbrook, Heather, Hu, David, Obeid, Wassim, Bhatraju, Pavan K., Ikizler, T. Alp, Siew, Edward D., Chinchilli, Vernon M., Garg, Amit X., Go, Alan S., Liu, Kathleen D., Kaufman, James S., Kimmel, Paul L., Himmelfarb, Jonathan, Coca, Steven G., Cantley, Lloyd G., and Parikh, Chirag R.

Abstract

Biomarkers of tubular function such as epidermal growth factor (EGF) may improve prognostication of participants at highest risk for chronic kidney disease (CKD) after hospitalization. To examine this, we measured urinary EGF (uEGF) from samples collected in the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study, a multi-center, prospective, observational cohort of hospitalized participants with and without AKI. Cox proportional hazards regression was used to investigate the association of uEGF/Cr at hospitalization, three months post-discharge, and the change between these time points with major adverse kidney events (MAKE): CKD incidence, progression, or development of kidney failure. Clinical findings were paired with mechanistic studies comparing relative Egfexpression in mouse models of kidney atrophy or repair after ischemia-reperfusion injury. MAKE was observed in 20% of 1,509 participants over 4.3 years of follow-up. Each 2-fold higher level of uEGF/Cr at three months was associated with decreased risk of MAKE (adjusted hazards ratio 0.46, 95% confidence interval: 0.39-0.55). Participants with the highest increase in uEGF/Cr from hospitalization to three-month follow-up had a lower risk of MAKE (adjusted hazards ratio 0.52; 95% confidence interval: 0.36-0.74) compared to those with the least change in uEGF/Cr. A model using uEGF/Cr at three months combined with clinical variables yielded moderate discrimination for MAKE (area under the curve 0.73; 95% confidence interval: 0.69-0.77) and strong discrimination for kidney failure at four years (area under the curve 0.96; 95% confidence interval: 0.92-1.00). Accelerated restoration of Egfexpression in mice was seen in the model of adaptive repair after injury, compared to a model of progressive atrophy. Thus, urinary EGF/Cr may be a biomarker of distal tubular health, with higher concentrations and increased uEGF/Cr post-discharge independently associated with reduced risk of MAKE in hospitalized patients.

Published
2023
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6. An atlas of healthy and injured cell states and niches in the human kidney

Author

Lake, Blue B., Menon, Rajasree, Winfree, Seth, Hu, Qiwen, Melo Ferreira, Ricardo, Kalhor, Kian, Barwinska, Daria, Otto, Edgar A., Ferkowicz, Michael, Diep, Dinh, Plongthongkum, Nongluk, Knoten, Amanda, Urata, Sarah, Mariani, Laura H., Naik, Abhijit S., Eddy, Sean, Zhang, Bo, Wu, Yan, Salamon, Diane, Williams, James C., Wang, Xin, Balderrama, Karol S., Hoover, Paul J., Murray, Evan, Marshall, Jamie L., Noel, Teia, Vijayan, Anitha, Hartman, Austin, Chen, Fei, Waikar, Sushrut S., Rosas, Sylvia E., Wilson, Francis P., Palevsky, Paul M., Kiryluk, Krzysztof, Sedor, John R., Toto, Robert D., Parikh, Chirag R., Kim, Eric H., Satija, Rahul, Greka, Anna, Macosko, Evan Z., Kharchenko, Peter V., Gaut, Joseph P., Hodgin, Jeffrey B., Eadon, Michael T., Dagher, Pierre C., El-Achkar, Tarek M., Zhang, Kun, Kretzler, Matthias, and Jain, Sanjay

Abstract

Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods1. Here we applied multiple single-cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). This has provided a high-resolution cellular atlas of 51 main cell types, which include rare and previously undescribed cell populations. The multi-omic approach provides detailed transcriptomic profiles, regulatory factors and spatial localizations spanning the entire kidney. We also define 28 cellular states across nephron segments and interstitium that were altered in kidney injury, encompassing cycling, adaptive (successful or maladaptive repair), transitioning and degenerative states. Molecular signatures permitted the localization of these states within injury neighbourhoods using spatial transcriptomics, while large-scale 3D imaging analysis (around 1.2 million neighbourhoods) provided corresponding linkages to active immune responses. These analyses defined biological pathways that are relevant to injury time-course and niches, including signatures underlying epithelial repair that predicted maladaptive states associated with a decline in kidney function. This integrated multimodal spatial cell atlas of healthy and diseased human kidneys represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

Published
2023
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7. Joint Modeling of Clinical and Biomarker Data in Acute Kidney Injury Defines Unique Subphenotypes with Differing Outcomes

Author

Vasquez-Rios, George, Oh, Wonsuk, Lee, Samuel, Bhatraju, Pavan, Mansour, Sherry G., Moledina, Dennis G., Gulamali, Faris F., Siew, Edward D., Garg, Amit X., Sarder, Pinaki, Chinchilli, Vernon M., Kaufman, James S., Hsu, Chi-yuan, Liu, Kathleen D., Kimmel, Paul L., Go, Alan S., Wurfel, Mark M., Himmelfarb, Jonathan, Parikh, Chirag R., Coca, Steven G., and Nadkarni, Girish N.

Published
2023
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8. The Society of Thoracic Surgeons/Society of Cardiovascular Anesthesiologists/American Society of Extracorporeal Technology Clinical Practice Guidelines for the Prevention of Adult Cardiac Surgery–Associated Acute Kidney Injury.

Author

Brown, Jeremiah R., Baker, Robert A., Shore-Lesserson, Linda, Fox, Amanda A., Mongero, Linda B., Lobdell, Kevin W., LeMaire, Scott A., De Somer, Filip M.J.J., Wyler von Ballmoos, Moritz, Barodka, Viachaslau, Arora, Rakesh C., Firestone, Scott, Solomon, Richard, Parikh, Chirag R., Shann, Kenneth G., and Hammon, John

Published
2023
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9. Characterization of Glomerular and Tubulointerstitial Proteomes in a Case of Nonsteroidal Anti-Inflammatory Drug–Attributed Acute Kidney Injury

Author

Parikh, Samir V., Madhavan, Sethu, Shapiro, John, Knight, Richard, Rosenberg, Avi Z., Parikh, Chirag R., Rovin, Brad, and Menez, Steven

Abstract

The major goals of the Kidney Precision Medicine Project (KPMPP) are to establish a molecular atlas of the kidney in health and disease and improve our understanding of the molecular drivers of CKD and AKI. In this clinical-pathologic-molecular correlation, we describe the case of a 38-year-old woman without any history of CKD who underwent a research kidney biopsy in the setting of AKI suspected to be due to nonsteroidal anti-inflammatory use after cesarean section delivery. The participant's histopathology was consistent with mild acute tubular injury, without significant interstitial fibrosis or tubular atrophy. This diagnosis was supported by analysis of the glomerular and tubulointerstitial proteomes. The proteomic interrogation revealed a molecular landscape that demonstrated differences in kidney prostaglandin synthesis that may be in response to nonsteroidal anti-inflammatory drugs and signs of intrarenal inflammation and fibrosis that were not evident by histopathology alone.

Published
2023
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10. Plasma Soluble Tumor Necrosis Factor Receptor Concentrations and Clinical Events After Hospitalization: Findings From the ASSESS-AKI and ARID Studies

Author

Coca, Steven G., Vasquez-Rios, George, Mansour, Sherry G., Moledina, Dennis G., Thiessen-Philbrook, Heather, Wurfel, Mark M., Bhatraju, Pavan, Himmelfarb, Jonathan, Siew, Eddie, Garg, Amit X., Hsu, Chi-yuan, Liu, Kathleen D., Kimmel, Paul L., Chinchilli, Vernon M., Kaufman, James S., Wilson, Michelle, Banks, Rosamonde E., Packington, Rebecca, McCole, Eibhlin, Kurth, Mary Jo, Richardson, Ciaran, Go, Alan S., Selby, Nicholas M., and Parikh, Chirag R.

Abstract

The role of plasma soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 in the prognosis of clinical events after hospitalization with or without acute kidney injury (AKI) is unknown.

Published
2023
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11. The Society of Thoracic Surgeons/Society of Cardiovascular Anesthesiologists/American Society for Extracorporeal Technology Clinical Practice Guidelines for the Prevention of Adult Cardiac Surgery–Associated Acute Kidney Injury

Author

Brown, Jeremiah R., Baker, Robert A., Shore-Lesserson, Linda, Fox, Amanda A., Mongero, Linda B., Lobdell, Kevin W., LeMaire, Scott A., De Somer, Filip M. J. J., Wyler von Ballmoos, Moritz, Barodka, Viachaslau, Arora, Rakesh C., Firestone, Scott, Solomon, Richard, Parikh, Chirag R., Shann, Kenneth G., and Hammon, John

Published
2023
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12. The Relationship between Rate and Volume of Intravenous Fluid Administration and Kidney Outcomes after Angiography

Author

Soomro, Qandeel H., Anand, Sonia T., Weisbord, Steven D., Gallagher, Martin P., Ferguson, Ryan E., Palevsky, Paul M., Bhatt, Deepak L., Parikh, Chirag R., Kaufman, James S., Brophy, Mary, Chertow, Glenn, Conner, Todd, Ferguson, Ryan, Fine, M., Kaufman, James, Lew, Robert, McCullough, Peter, Palevsky, Paul, Parikh, Chirag, Ringer, Robert, Shunk, Kendrick, Soliva, Susan, Weisbord, Steven, Bhatt, Deepak, Cass, Alan, Gallagher, Martin, McFalls, Edward, Pirakh, Chirag, Wu, Hongsheng, Ratliff, Michelle, Ketteler, Erika, Goff, James, Snider, Richard, Jones, Debra, Kreuch, Jeannie, Duvernoy, Claire, Thomas, Michael, Willatt, Jonathan, Gurm, Hitinder, Krishnamurthy, Venkat, Nallamothu, Brahmajee, Szymanski, Kendra, Grossman, P. Michael, Menees, Daniel, Rose, Patricia, Mavromatis, Kreton, Kumar, Gautam, Raghavan, Sumati, Dow, Jeanne, Mandawat, Mahendra, Noe, Susan, Alavi, Hossain, Calkins, Joe, McNear, Jennifer, Beals, Donald, Cavalieri, Stuart, Sierzega, Renata, Pearson, Laura, Afaq, Mazhar, Vaitkus, Paul, Kudryk, Bruce, Hall, Dennis, Nadella, Neelima, Corin, William, Woklu, Nina, Inting-Toothman, Stella, Wescott, Lea, Ventura, Nicole, Kinlay, Scott, Croce, Kevin, Faxon, David, Vokonas, Pantel, Raffetto, Joseph, McPhee, James, Gupta, Naren, Nava, Adrianna, Ly, Samantha, My-Do, Jacquelyn, Ostrowski, Simon, Bundy, Mariah, Quinn, Margot, Chin, Melissa, Corbelli, John, Dosluoglu, Hasan, Lohr, James, Rivero, Mariel, Cooke, Beth, Galla, Ann, Cloen, Denise, Fernandes, Valerian, DiBona, Alexander, Nielsen, Christopher, Idleman, Lois, Lee, Bertha, Vidovich, Mladen, Kibbe, Melina, Griza, Decebal, Raicu, Mihai, Rothenberg, Florence, Thakar, Charuhas, Madabhushi, Aditi, Arif, Imran, Bath, Jonathan, Helmy, Tarek, Unterbrink, Kendra, Ross, Stephanie, Bailey, Cathy, Hailes, Myrtle, Goldberg, Jonathan, Jozic, Joseph, Kang, Preet, Kalman, Jeaniene, Rosenthal, Noah, Catania, Deborah, Marlow, Jeanne, Kumaran, Vinay, Krupka, Angela, Zappernick, Taissa, Brilakis, Emmanouil, Tsai, Shirling, Banerjee, Subhash, Modrall, J. Gregory, Roesle, Michele, Hamilton, Marcie, Lusk, Cassie, Compton, Jennifer, Willis, Cyenthia, Atwell, Amy, Soto-Gonzalez, Marilisa, Agarwal, Ajay, Saklayen, Mohammad, Woerner, Donna, Ross, Jeffrey, Turner, Karen, Zheng-Phelan, Ling, Rider, Kamia, Rao, Sunil, Jones, W. Schuyler, Povsic, Thomas, Krucoff, Mitchell, Brennan, James, Miller, Michael, Mureebe, Leila, Aristy, Kathy, Powell, Marilyn, Bavry, Anthony, Choi, Calvin, Park, Ki, Curry, Tempa, Robertson, Debra, Wright, Cila, Jneid, Hani, Paniagua, David, Denktas, Ali, Lara-Smalling, Agueda, Palmer, Leah, Malarchick, Jo Ann, Broussard, Emily, Bolad, Islam, Breall, Jeffrey, Motaganahalli, Raghunandan, English, Beth, Ramkaransingh, Jeffrey, Mukerji, Rita, Subbarao, Roopa, Williams, Vicki, Henson, Sharon, Krier, Connie, Parashara, Deepak, Ciniglio, Ricardo, Barua, Rajat, Roys, Michael, Surineni, Kamalakar, Mendes, Kimberley, Oni, Olurinde, Uretsky, Barry, Ahmed, Zubair, Yousaf, Muhammad, Hakeem, Abdul, Chung, Hui Yong, Miller, Kristin, Dishongh, Katherine, Ramanathan, Kodangudi, Shah, Rahman, McGee, Jesse, Qualls, Zoe, Armstrong, Ashley, Johnson, Lillie, Garcia, Santiago, Adabag, Selcuk, Vakil, Kairav, Nguyen, Jennifer, Berg, Matthew, Herrmann, Rebekah, Condon, Debra, Meyeraan, Tacy, Sedlis, Steven, Lorin, Jeffrey, Keary, Mary, Shah, Binita, Maranan, Leandro, Latif, Faisal, Thadani, Udho, Abu-Fadel, Mazen, Exaire, Jose, Rousan, Talla, Ramirez-Jimenez, Arleen, Pham, Trang, Giacomini, John, Lit, Yiming, Massaband, Payam, Yong, Celina, Fearon, William, Zhou, Wei, Aalami, Oliver, Peters, Theresa, Bratcher, Karen, Monteverde, Edgardo, Rahman, Aref, Bandi, Rupal, Garbelotti, Kelly, Mulukutla, Suresh, Overberger, Pamela, Watnick, Suzanne, Davies, Crispin, Larsen, Greg, Atkinson, Tamara, Walczyk, Jacqueline, Kenworthy-Heinige, Tawni, Guenther, Stephanie, Pitts, Alexandra, Jovin, Ion, Minisi, Anthony, Sumption, Kevin, Feldman, George, Ha, Jonathan, Hendrix, Mack, Maldonado, Maureen, Jeter, Deborah, Klein, Andrew, Forsberg, Michael, Rowe, Caroline, Nasir, Ammar, Mani, Kartik, Vercher, Paul, Waidmann, Kristi, Vargo, Kristin, Chilakapati, Venkata, Jarmukli, Nabil, Tan, Shen-Li, Sherigar, Rathnakara, Bottomley, Sharon, Capuno, Maribeth, Henley, Katherine, Dev, Devasmita, Mathew, Jacob, Ochalek, Tracy, Lui, Charles, Smith, Brigham, Huo, Eugene, Frodsham, Aaron, Eskelson, Noni, Velarde, Kandi, Dulin, Heather, Martinez, Lillian, Zimmet, Jeffrey, Sawhney, Rajiv, Malik, Fady, Chou, Tony, Huynh, Cynthia, Stanley, Kathleen, Garcia, Epifanio, Lehmann, Kenneth, Stadius, Michael, Beatty, Alexis, Naria, Sohilkumar, Galvin, Georgia, Chilton, Robert, Pham, Son, Oliveros, Rene, Hecht, Joan, Thai, Hoang, Truong, Huu Tam, Goldman, Steven, Thal, Sergio, Juneman, Elizabeth, Kapoor, Divya, Tsuda, Ryan, Kipps, Juliana, Mikhail, Amani, Sandoval, Michael, Currier, Jesse, Lee, Hsin-Yi, Chang, Donald, Walsworth, Matthew, Warner, Alberta, Chen, Alice, Lendvai, Dora, Johnson, Janet, Lee, Joanne, Coggan, Sarah, Kumar, Namrata Nath, Dempsey, Erika, Kotwal, Sradha, Smyth, Brendan, Yianni, Alexia, Lee, Li Hui, Cheong, Siew Yan, Yates, Casey, James, Earl, Talaulikar, Girish, Farshid, Ahmad, Johnson, Patricia, Taverner, Pearle, Chadwick, Heather, Stewart, Ralph, Benatar, Jocelyne, Stone, Louise, Howell, Leah, Anderson, Sue, Lehnhard, Siobhan, Patten, Cathrine, Farouque, Omar, Bellomo, Rinaldo, Horrigan, Mark, Scott, Peter, Jones, Nicolas, Yudi, Matias, Huq, Rafi, Al-Fiadh, Ali, Brown, Louise, Brieger, David, Hillis, Graham, Cherry, Jonathan, Aitken, Sarah, Anastasius, Malcom, Lau, Jerrett, Lowe, Harry, Ayoub, Chadi, Jardine, Meg, O?Connor, Jody, Wong, Christopher, Wu, June, Xu, Kitty, Webster, Julie, Mwaijele, Liliang, Hand, Samantha, Chew, Derek, Alyward, Philip, Balakrishnan, Deepu, Prakash, Roshan, Pathik, Bhupesh, Kinatra, Vineet, Jones, Dylan, Singh, Arun, Ratib, Karim, Hammad, Nassser Al, Gunton, James, Mazhar, Jawad, Musameh, Muntaser, O?Shea, Catherine, Judd, Jo, Raman, Betty, Wollaston, Fiona, Felice, Kerri Ann, Hincks, Christine, Harrison, Timothy, Fawcett, Malcolm, Wright, Therese, Horsfall, Lee-Anne, Kissajukian, Francis, Murphy, Diedre, Bartlett, Pamela, Stockle, Paul, William, Maged, Elsokkari, Ihab, Rangasamy, Karthikeyan, Roy, Probal, Tran, David, Hayat, Muhammed Umair, May, Austin, Nyakudarika, Elijah, Phang, Calvin, Conway, Bets, O?Donoghue, Michelle, Ellis, Katrina, Kanna, Rajesh, Hendriks, Randall, Forrest, Nicole, Tulloch, Gill, Greenwell, Della, Ghapar, Abd Kahar, Ghani, Abdul Raqib Abd, Sundaralingam, Shamini, Fuah, K., Habizal, Nor Halwani, Daud, Siti Rohaya, Haq, Hafsah Begum binti Abdul, Mohammad, Masliza Binti, Hassan, Faizah Che, Hashim, Hanani, Ismail, Omar, Kong, Poi Keong, Ma, Soot Keng, Wahab, Mohamed Jahangir Abdul, Abdulla, Zarina Banu, Kader, Mohamad Ali Sheikh Abdul, Goh, Chong Aik, Ahmadsha, Shahul Hamid, Naser, Mohamad Nazrulhisham Mad, Yusuf, Azizah, Govindasamy, Paramesveri, Ibrahim, Nur Azliati Binti, Yahaya, Normilah, Juergens, Craig, French, John, Mussap, C., Lo, Sidney, Burgess, S., Mallard, Trevor, Huang, Justin, Kumar, Manish, Lee, Adam, Leung, Dominic, Badie, Tamar, Xu, James, Terluk, Andrew, Croucher, Alexandria, O?Brien, Kelsey, Raynes, Suzanne, Plotz, Maria, Hallani, Hisham, Fernandes, Clyne, Fitzpatrick, Drew, Parikh, Devang, Coulshed, David, Pathan, Faraz, Ganda, Prashil, Chandrala, Pavan, Barry, Lisa, Mackenzie, Michele, VanGaal, William, Hyat, Umair, Tsay, It Men, Subiakto, Ivan, Cresp, Damian, Nelson, Gregory, Mau, James, Shaw, Elizabeth, Yan, Warren, Arena, Frank, Danson, Edward, Vernon, S., Ward, Michael, Allahwala, U., Reid, Emma, Straiton, Nicola, Whitley, Alexandra, Loxton, Annie, Erickson, Royal Perth Hospital: Matthew, Ihdayid, Abdul-Rhman, Dias, Peter, Atique, Syed, Bonner, Michelle, Venn-Edmonds, Clare, Prasan, Ananth, Sader, Mark, Ramsay, David, Ford, Tom, Weaver, James, Binnekamp, Maurits, Barrett, David, Roy, James, Ng, Ben, Youssef, George, Shrestha, Prakriti, Vrachas, Deborah, Dobinson, Kate, Ternouth, Ian, Lumb, Nicky, Sebastian, Jeffrey, Jackson, Carolyn, Vickers, Cathy, Prideaux, Jan, Ahmad, Wan Azman Wan, Abidin, Imran Zainal, Zuhdi, Ahmad Syadi Mahmood, Ismail, Muhammad Dzafir, Sridhar, Ganiga Srinivasaiah, Lim, Soo Kun, Hadi, Moud Firdaus, Adnan, Wan Ahmad Hafiz Wan Md, Kassim, Zainab Abu, Mansor, Syed Mukhtar Syed, Lee, Vin-Zhen, Harding, Scott, Ranchord, Anil, Matsis, Philip, Aitken, Andrew, Simmonds, Mark Bernard, Fairley, Sarah, Wolbinski, Mariusz, Plunkett, Susan, Sinan, Ali Al, Ferrier, Katherine, O?Meeghan, Tim, Wilkins, Ben, Anscomise, Russell, Sasse, Alexander, Kirby, Alyssa, Ershad, Shakiya, Smyth, Duncan, Lim, Ren Yik, Middleditch, Diane, and Davies, Bronwyn

Published
2022
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14. Systematic Review and Meta-Analysis of Plasma and Urine Biomarkers for CKD Outcomes

Author

Liu, Caroline, Debnath, Neha, Mosoyan, Gohar, Chauhan, Kinsuk, Vasquez-Rios, George, Soudant, Celine, Menez, Steve, Parikh, Chirag R., and Coca, Steven G.

Abstract

Biomarker studies in the setting of CKD have increased considerably within the past 15 years, but vary significantly by design and clinical context. The authors conducted a systematic review and meta-analysis to summarize the prognostic value of preclinical plasma and urine biomarkers for CKD outcomes (incident CKD, CKD progression, or incident ESKD), including 129 studies in the meta-analysis. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) among some of the most studied CKD biomarkers were 2.17 (95% CI, 1.91 to 2.47) for plasma TNFR1, 1.21 (95% CI, 1.15 to 1.28) for plasma FGF23, 2.07 (95% CI, 1.82 to 2.34) for plasma TNFR2, 1.10 (95% CI, 1.05 to 1.16) for urine KIM-1, and 1.12 (95% CI, 1.06 to 1.19) for urine NGAL. The study?s findings suggest these biomarkers merit assessment of their performance in clinical practice.

Published
2022
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15. Comparison of proteomic methods in evaluating biomarker-AKI associations in cardiac surgery patients.

Author

Liu, Richard X., Thiessen-Philbrook, Heather R., Vasan, Ramachandran S., Coresh, Josef, Ganz, Peter, Bonventre, Joseph V., Kimmel, Paul L., and Parikh, Chirag R.

Abstract

Although immunoassays are the most widely used protein measurement method, aptamer-based methods such as the SomaScan platform can quantify up to 7000 proteins per biosample, creating new opportunities for unbiased discovery. However, there is limited research comparing the consistency of biomarker-disease associations between immunoassay and aptamer-based platforms. In a substudy of the TRIBE-AKI cohort, preoperative and postoperative plasma samples from 294 patients with previous immunoassay measurements were analyzed using the SomaScan platform. Inter-platform Spearman correlations (rs) and biomarker-AKI associations were compared across 30 preoperative and 34 postoperative immunoassay-aptamer pairs. Possible factors contributing to inter-platform differences were examined including target protein characteristics, immunoassay, and SomaScan coefficients of variation, other assay characteristics, and sample storage time. The median rs was 0.54 (interquartile range [IQR] 0.34-0.83) in postoperative samples and 0.41 (IQR 0.21-0.69) in preoperative samples. We observed a trend of greater rs in biomarkers with greater concentrations; the Spearman correlation between the concentration of protein and the inter-platform correlation was 0.64 in preoperative pairs and 0.53 in postoperative pairs. Of proteins measured by immunoassays, we observed significant biomarker-AKI associations for 13 proteins preop and 24 postop; of all corresponding aptamers, 8 proteins preop and 12 postop. All proteins significantly associated with AKI as measured by SomaScan were also significantly associated with AKI as measured by immunoassay. All biomarker-AKI odds ratios were significantly different (P < 0.05) between platforms in 14% of aptamer-immunoassay pairs, none of which had high (rs > 0.50) inter-platform correlations. Although similar biomarker-disease associations were observed overall, biomarkers with high physiological concentrations tended to have the highest-confidence inter-platform operability in correlations and biomarker-disease associations. Aptamer assays provide excellent precision and an unprecedented coverage and promise for disease associations but interpretation of results should keep in mind a broad range of correlations with immunoassays. [ABSTRACT FROM AUTHOR]

Published
2021
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16. Acute Kidney Injury Associates with Long-Term Increases in Plasma TNFR1, TNFR2, and KIM-1: Findings from the CRIC Study

Author

McCoy, Ian E., Hsu, Jesse Y., Bonventre, Joseph V., Parikh, Chirag R., Go, Alan S., Liu, Kathleen D., Ricardo, Ana C., Srivastava, Anand, Cohen, Debbie L., He, Jiang, Chen, Jing, Rao, Panduranga S., Hsu, Chi-yuan, Appel, Lawrence J., Feldman, Harold J., Lash, James P., Nelson, Robert G., Rahman, Mahboob, Shah, Vallabh O., and Unruh, Mark L.

Abstract

Levels of TNF receptors 1 and 2 (TNFR1 and TNFR2) and kidney injury molecule 1 (KIM-1) vary considerably among patients with CKD; those with higher levels have faster subsequent disease progression. The reasons why some individuals have higher levels of biomarkers of inflammation and injury are unknown. In this observational cohort study, the authors investigated whether these higher biomarker levels reflect effects of prior episodes of AKI. They found that levels of TNFR1, TNFR2, and KIM-1 in banked plasma samples increased after AKI, and these elevations persist for months, a longer timeframe than examined in prior studies. These findings may provide insight into the pathophysiology of kidney disease progression and the potential role of AKI episodes punctuating the course of CKD.

Published
2022
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17. Longitudinal TNFR1 and TNFR2 and Kidney Outcomes: Results from AASK and VA NEPHRON-D

Author

Chen, Teresa K., Coca, Steven G., Estrella, Michelle M., Appel, Lawrence J., Coresh, Josef, Thiessen Philbrook, Heather, Obeid, Wassim, Fried, Linda F., Heerspink, Hiddo J.L., Ix, Joachim H., Shlipak, Michael G., Kimmel, Paul L., Parikh, Chirag R., Grams, Morgan E., Ramachandran, Vasan S., Massaro, Joseph, Clish, Clary, Schelling, Jeffrey, Denburg, Michelle, Furth, Susan, Warady, Bradley, Bonventre, Joseph, Waikar, Sushrut, McMahon, Gearoid, Sabbisetti, Venkata, Coresh, Josef, Grams, Morgan, Rebholz, Casey, Abraham, Alison, Tin, Adrienne, Parikh, Chirag, Klein, Jon, Coca, Steven, Ferket, Bart S, Nadkarni, Girish N., Rhee, Eugene, Kimmel, Paul L., Gossett, Daniel, Rovin, Brad, Shlipak, Michael G., Sarnak, M, Levey, Andrew S., Inker, Lesley A., Foster, Meredith, Guti?rrez, Orlando M., Ix, Joachim, Dubin, Ruth, Seegmiller, Jesse, Hostetter, Tom, Deo, Rajat, Feldman, Harold I., Anderson, Amanda, Mifflin, Theodore, Xie, Dawei, Shou, Haochang, Ballard, Shawn, Whitehead, Krista, Collins, Heather, Greenberg, Jason, and Ganz, Peter

Abstract

Recent research suggests that biomarkers of the TNF pathway (TNFR1 and TNFR2) are associated with worse kidney outcomes. Most of these studies, however, evaluated baseline levels rather than longitudinal changes. In two cohorts (AASK, which enrolled Black people with CKD attributed to hypertension, and VA NEPHRON-D, which enrolled veterans with albuminuric CKD and type 2 diabetes), greater longitudinal increases in serum or plasma TNFR1 and TNFR2 were associated with higher risks of ESKD in AASK and subsequent kidney function decline in VA NEPHRON-D. These associations were independent of baseline biomarker level and kidney function. Longitudinal trajectories in TNFR1 and TNFR2 may ultimately allow improved risk assessment for kidney failure in persons with CKD.

Published
2022
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19. Trends in the procurement and discard of kidneys from deceased donors with acute kidney injury

Author

Liu, Caroline, Alasfar, Sami, Reese, Peter P., Mohan, Sumit, Doshi, Mona D., Hall, Isaac E., Thiessen Philbrook, Heather, Jia, Yaqi, Stewart, Darren, and Parikh, Chirag R.

Abstract

Kidney allocation trends from deceased donors with acute kidney injury (AKI) have not been characterized since initial Kidney Donor Profile Index reporting in 2012 and its use under the revised Kidney Allocation System (KAS) in 2014. We conducted a retrospective analysis of US registry data to characterize kidney procurement and discard trends in deceased donors with AKI, defined by ≥50% or ≥0.3 mg/dl (≥4.0 mg/dl or ≥200% for stage 3) increase in terminal serum creatinine from admission. From 2010 to 2020, 172 410 kidneys were procured from 93 341 deceased donors 16 years or older; 34 984 kidneys were discarded (17 559 from AKI donors). The proportion of stage 3 AKI donors doubled from 6% (412/6841) in 2010 to 12% (1365/11493) in 2020. Procurement of stage 3 AKI kidneys increased from 51% (423/824) to 80% (2183/2730). While discard of stage 3 AKI kidneys increased from 41% (175/423) in 2010 to 44% (960/2183) in 2020, this increase was not statistically significant in interrupted time-series analysis following KAS implementation (slope difference −0.41 [−3.22, 2.4], and level change 3.09 [−6.4, 12.6]). In conclusion, the absolute number of stage 3 AKI kidneys transplanted has increased. Ongoing high discard rates of these kidneys suggest opportunities for improved utilization.

Published
2022
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21. Angiopoietins as Prognostic Markers for Future Kidney Disease and Heart Failure Events after Acute Kidney Injury

Author

Mansour, Sherry G., Bhatraju, Pavan K., Coca, Steven G., Obeid, Wassim, Wilson, Francis P., Stanaway, Ian B., Jia, Yaqi, Thiessen-Philbrook, Heather, Go, Alan S., Ikizler, T. Alp, Siew, Edward D., Chinchilli, Vernon M., Hsu, Chi-yuan, Garg, Amit X., Reeves, W. Brian, Liu, Kathleen D., Kimmel, Paul L., Kaufman, James S., Wurfel, Mark M., Himmelfarb, Jonathan, Parikh, Samir M., and Parikh, Chirag R.

Abstract

Mechanisms underlying long-term effects after AKI remain unclear. Because vessel instability is an early response to endothelial injury, the authors studied markers of blood vessel homeostasis (the plasma angiopoietins angiopoietin-1 and angiopoietin-2) in a multicenter prospective cohort that included 1503 adults, half of whom had AKI. Three months after hospitalization, the highest quartile of plasma angiopoietin-1:angiopoietin-2 ratio compared with the lowest quartile associated with 72% less risk of CKD progression, 94% less risk of heart failure, and 82% less risk of death among those with AKI; those without AKI exhibited similar but less pronounced reductions in risk of heart failure and mortality. Angiopoietins may serve as a common pathway to explain the progression of kidney and heart disease after AKI and may point to potential future interventions.

Published
2022
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22. Trends in the procurement and discard of kidneys from deceased donors with acute kidney injury

Author

Liu, Caroline, Alasfar, Sami, Reese, Peter P., Mohan, Sumit, Doshi, Mona D., Hall, Isaac E., Thiessen Philbrook, Heather, Jia, Yaqi, Stewart, Darren, and Parikh, Chirag R.

Abstract

Kidney allocation trends from deceased donors with acute kidney injury (AKI) have not been characterized since initial Kidney Donor Profile Index reporting in 2012 and its use under the revised Kidney Allocation System (KAS) in 2014. We conducted a retrospective analysis of US registry data to characterize kidney procurement and discard trends in deceased donors with AKI, defined by ≥50% or ≥0.3 mg/dl (≥4.0 mg/dl or ≥200% for stage 3) increase in terminal serum creatinine from admission. From 2010 to 2020, 172 410 kidneys were procured from 93 341 deceased donors 16 years or older; 34 984 kidneys were discarded (17 559 from AKI donors). The proportion of stage 3 AKI donors doubled from 6% (412/6841) in 2010 to 12% (1365/11493) in 2020. Procurement of stage 3 AKI kidneys increased from 51% (423/824) to 80% (2183/2730). While discard of stage 3 AKI kidneys increased from 41% (175/423) in 2010 to 44% (960/2183) in 2020, this increase was not statistically significant in interrupted time‐series analysis following KAS implementation (slope difference −0.41 [−3.22, 2.4], and level change 3.09 [−6.4, 12.6]). In conclusion, the absolute number of stage 3 AKI kidneys transplanted has increased. Ongoing high discard rates of these kidneys suggest opportunities for improved utilization. Retrospective analysis of OPTN data from 2010 to 2020 shows increases in both the recovery and discard rates of kidneys from deceased donors with stage 3 acute kidney injury and a concurrent increase in the absolute number of transplants utilizing these kidneys.

Published
2022
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24. The Association between Cytokines and 365-Day Readmission or Mortality in Adult Cardiac Surgery

Author

Everett, Allen D., Alam, Shama S., Owens, Sherry L., Parker, Devin M., Goodrich, Christine, Likosky, Donald S., Thiessen-Philbrook, Heather, Wyler von Ballmoos, Moritz, Lobdell, Kevin, MacKenzie, Todd A., Jacobs, Jeffrey, Parikh, Chirag R., DiScipio, Anthony W., Malenka, David J., Brown, Jeremiah R., Everett, Allen D., Alam, Shama S., Owens, Sherry L., Parker, Devin M., Goodrich, Christine, Likosky, Donald S., Thiessen-Philbrook, Heather, Wyler von Ballmoos, Moritz, Lobdell, Kevin, MacKenzie, Todd A., Jacobs, Jeffrey, Parikh, Chirag R., DiScipio, Anthony W., Malenka, David J., and Brown, Jeremiah R.

Abstract

Cardiac surgery results in a multifactorial systemic inflammatory response with inflammatory cytokines, such as interleukin-10 and 6 (IL-10 and IL-6), shown to have potential in the prediction of adverse outcomes including readmission or mortality. This study sought to measure the association between IL-6 and IL-10 levels and 1-year hospital readmission or mortality following cardiac surgery. Plasma biomarkers IL-6 and IL-10 were measured in 1,047 patients discharged alive after isolated coronary artery bypass graft surgery from eight medical centers participating in the Northern New England Cardiovascular Disease Study Group between 2004 and 2007. Readmission status and mortality were ascertained using Medicare, state all-payer claims, and the National Death Index. We evaluated the association between preoperative and postoperative cytokines and 1-year readmission or mortality using Kaplan–Meier estimates and Cox’s proportional hazards modeling, adjusting for covariates used in the Society of Thoracic Surgeons 30-day readmission model. The median follow-up time was 1 year. After adjustment, patients in the highest tertile of postoperative IL-6 values had a significantly increased risk of readmission or death within 1 year (HR: 1.38; 95% CI: 1.03–1.85), and an increased risk of death within 1 year of discharge (HR: 4.88; 95% CI: 1.26–18.85) compared with patients in the lowest tertile. However, postoperative IL-10 levels, although increasing through tertiles, were not found to be significantly associated independently with 1-year readmission or mortality (HR: 1.25; 95% CI: .93–1.69). Pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10 may be postoperative markers of cardiac injury, and IL-6, specifically, shows promise in predicting readmission and mortality following cardiac surgery.

Published
2019
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30. Urine Biomarkers of Kidney Tubule Health, Injury, and Inflammation are Associated with Progression of CKD in Children

Author

Greenberg, Jason H., Abraham, Alison G., Xu, Yunwen, Schelling, Jeffrey R., Feldman, Harold I., Sabbisetti, Venkata S., Ix, Joachim H., Jogalekar, Manasi P., Coca, Steven, Waikar, Sushrut S., Shlipak, Michael G., Warady, Bradley A., Vasan, Ramachandran S., Kimmel, Paul L., Bonventre, Joseph V., Denburg, Michelle, Parikh, Chirag R., Furth, Susan, Ramachandran, Vasan S., Schelling, Jeffrey, Denburg, Michelle, Furth, Susan, Warady, Bradley, Bonventre, Joseph, Waikar, Sushrut, Sabbisetti, Venkata, Coresh, Josef, Grams, Morgan, Rebholz, Casey, Abraham, Alison, Parikh, Chirag, Coca, Steven, Rhee, Eugene, Kimmel, Paul L., Kusek, John W., Rovin, Brad, Shlipak, Michael G., Sarnak, Mark, Gutiérrez, Orlando M., Ix, Joachim, Dubin, Ruth, Hostetter, Tom, Deo, Rajat, Feldman, Harold I., Xie, Dawei, Shou, Haochang, Ballard, Shawn, Whitehead, Krista, Collins, Heather, Greenberg, Jason H., and Ganz, Peter

Published
2021
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31. Identification of Distinct Clinical Subphenotypes in Critically Ill Patients With COVID-19

Author

Vasquez, Charles R., Gupta, Shruti, Miano, Todd A., Roche, Meaghan, Hsu, Jesse, Yang, Wei, Holena, Daniel N., Reilly, John P., Schrauben, Sarah J., Leaf, David E., Shashaty, Michael G.S., Walther, Carl P., Anumudu, Samaya J., Arunthamakun, Justin, Kopecky, Kathleen F., Milligan, Gregory P., McCullough, Peter A., Nguyen, Thuy-Duyen, Shaefi, Shahzad, Krajewski, Megan L., Shankar, Sidharth, Pannu, Ameeka, Valencia, Juan D., Waikar, Sushrut S., Kibbelaar, Zoe A., Athavale, Ambarish M., Hart, Peter, Upadhyay, Shristi, Vohra, Ishaan, Oyintayo, Ajiboye, Green, Adam, Rachoin, Jean-Sebastien, Schorr, Christa A., Shea, Lisa, Edmonston, Daniel L., Mosher, Christopher L., Shehata, Alexandre M., Cohen, Zaza, Allusson, Valerie, Bambrick-Santoyo, Gabriela, Bhatti, Noor ul aain, Mehta, Bijal, Williams, Aquino, Brenner, Samantha K., Walters, Patricia, Go, Ronaldo C., Rose, Keith M., Chan, Lili, Mathews, Kusum S., Coca, Steven G., Altman, Deena R., Saha, Aparna, Soh, Howard, Wen, Huei Hsun, Bose, Sonali, Leven, Emily A., Wang, Jing G., Mosoyan, Gohar, Nadkarni, Girish N., Pattharanitima, Pattharawin, Gallagher, Emily J., Friedman, Allon N., Guirguis, John, Kapoor, Rajat, Meshberger, Christopher, Kelly, Katherine J., Parikh, Chirag R., Garibaldi, Brian T., Corona-Villalobos, Celia P., Wen, Yumeng, Menez, Steven, Malik, Rubab F., Cervantes, Carmen Elena, Gautam, Samir C., Mallappallil, Mary C., Ouyang, Jie, John, Sabu, Yap, Ernie, Melaku, Yohannes, Mohamed, Ibrahim, Bajracharya, Siddhartha, Puri, Isha, Thaxton, Mariah, Bhattacharya, Jyotsna, Wagner, John, Boudourakis, Leon, Nguyen, H. Bryant, Ahoubim, Afshin, Kashani, Kianoush, Tehranian, Shahrzad, Thomas, Leslie F., Sirganagari, Dheeraj Reddy, Guru, Pramod K., Zhou, Yan, Bergl, Paul A., Rodriguez, Jesus, Shah, Jatan A., Gupta, Mrigank S., Kumar, Princy N., Lazarous, Deepa G., Kassaye, Seble G., Melamed, Michal L., Johns, Tanya S., Mocerino, Ryan, Prudhvi, Kalyan, Zhu, Denzel, Levy, Rebecca V., Azzi, Yorg, Fisher, Molly, Yunes, Milagros, Sedaliu, Kaltrina, Golestaneh, Ladan, Brogan, Maureen, Kumar, Neelja, Chang, Michael, Thakkar, Jyotsana, Raichoudhury, Ritesh, Athreya, Akshay, Farag, Mohamed, Schenck, Edward J., Cho, Soo Jung, Plataki, Maria, Alvarez-Mulett, Sergio L., Gomez-Escobar, Luis G., Pan, Di, Lee, Stefi, Krishnan, Jamuna, Whalen, William, Charytan, David, Macina, Ashley, Chaudhry, Sobaata, Wu, Benjamin, Modersitzki, Frank, Srivastava, Anand, Leidner, Alexander S., Martinez, Carlos, Kruser, Jacqueline M., Wunderink, Richard G., Hodakowski, Alexander J., Velez, Juan Carlos Q., Price-Haywood, Eboni G., Matute-Trochez, Luis A., Hasty, Anna E., Mohamed, Muner M.B., Avasare, Rupali S., Zonies, David, Leaf, David E., Gupta, Shruti, Sise, Meghan E., Newman, Erik T., Omar, Samah Abu, Pokharel, Kapil K., Sharma, Shreyak, Singh, Harkarandeep, Correa, Simon, Shaukat, Tanveer, Kamal, Omer, Wang, Wei, Yang, Heather, Boateng, Jeffery O., Lee, Meghan, Strohbehn, Ian A., Li, Jiahua, Mueller, Ariel L., Redfern, Roberta E., Cairl, Nicholas S., Naimy, Gabriel, Abu-Saif, Abeer, Hall, Danyell, Bickley, Laura, Rowan, Chris, Madhani-Lovely, Farah, Peev, Vasil, Reiser, Jochen, Byun, John J., Vissing, Andrew, Kapania, Esha M., Post, Zoe, Patel, Nilam P., Hermes, Joy-Marie, Sutherland, Anne K., Patrawalla, Amee, Finkel, Diana G., Danek, Barbara A., Arikapudi, Sowminya, Paer, Jeffrey M., Cangialosi, Peter, Liotta, Mark, Radbel, Jared, Puri, Sonika, Sunderram, Jag, Scharf, Matthew T., Ahmed, Ayesha, Berim, Ilya, Vatson, Jayanth S., Anand, Shuchi, Levitt, Joseph E., Garcia, Pablo, Boyle, Suzanne M., Song, Rui, Zhang, Jingjing, Woo, Sang Hoon, Deng, Xiaoying, Katz-Greenberg, Goni, Senter, Katharine, Sharshir, Moh’d A., Rusnak, Vadym V., Ali, Muhammad Imran, Bansal, Anip, Podoll, Amber S., Chonchol, Michel, Sharma, Sunita, Burnham, Ellen L., Rashidi, Arash, Hejal, Rana, Judd, Eric, Latta, Laura, Tolwani, Ashita, Albertson, Timothy E., Adams, Jason Y., Chang, Steven Y., Beutler, Rebecca M., Schulze, Carl E., Macedo, Etienne, Rhee, Harin, Liu, Kathleen D., Jotwani, Vasantha K., Koyner, Jay L., Kunczt, Alissa, Shah, Chintan V., Jaikaransingh, Vishal, Toth-Manikowski, Stephanie M., Joo, Min J., Lash, James P., Neyra, Javier A., Chaaban, Nourhan, Ahmad, Yahya, Elias, Madona, Dy, Rajany, Iardino, Alfredo, Au, Elizabeth H., Sharma, Jill H., Sosa, Marie Anne, Taldone, Sabrina, Contreras, Gabriel, De La Zerda, David, Gershengorn, Hayley B., Hayek, Salim S., Blakely, Pennelope, Berlin, Hanna, Azam, Tariq U., Shadid, Husam, Pan, Michael, Hayer, Patrick O’, Meloche, Chelsea, Feroze, Rafey, Kaakati, Rayan, Perry, Danny, Bitar, Abbas, Anderson, Elizabeth, Padalia, Kishan J., Donnelly, John P., Admon, Andrew J., Flythe, Jennifer E., Tugman, Matthew J., Chang, Emily H., Brown, Brent R., Leonberg-Yoo, Amanda K., Spiardi, Ryan C., Miano, Todd A., Roche, Meaghan S., Vasquez, Charles R., Bansal, Amar D., Ernecoff, Natalie C., Kapoor, Sanjana, Verma, Siddharth, Chen, Huiwen, Kovesdy, Csaba P., Molnar, Miklos Z., Azhar, Ambreen, Hedayati, S. Susan, Nadamuni, Mridula V., Shastri, Shani, Willett, Duwayne L., Short, Samuel A.P., Renaghan, Amanda D., Enfield, Kyle B., Bhatraju, Pavan K., Malik, A. Bilal, Semler, Matthew W., Vijayan, Anitha, Joy, Christina Mariyam, Li, Tingting, Goldberg, Seth, Kao, Patricia F., Schumaker, Greg L., Goyal, Nitender, Faugno, Anthony J., Schumaker, Greg L., Hsu, Caroline M., Tariq, Asma, Meyer, Leah, Kshirsagar, Ravi K., Weiner, Daniel E., Jose, Aju, Christov, Marta, Griffiths, Jennifer, Gupta, Sanjeev, Kapoor, Aromma, Chugh, Savneek, Wilson, Perry, Arora, Tanima, and Ugwuowo, Ugochukwu

Abstract

Subphenotypes have been identified in patients with sepsis and ARDS and are associated with different outcomes and responses to therapies.

Published
2021
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33. Cardiac Biomarkers for Risk Stratification of Acute Kidney Injury After Pediatric Cardiac Surgery.

Author

Greenberg, Jason H., Parsons, Michael, Zappitelli, Michael, Jia, Yaqi, Thiessen-Philbrook, Heather R., Devarajan, Prasad, Everett, Allen D., and Parikh, Chirag R.

Abstract

Children undergoing a cardiac surgical procedure are at increased risk for acute kidney injury (AKI). Novel biomarkers are needed to improve risk stratification of AKI after cardiac surgery. We enrolled children aged 1 month to 18 years old from July 2007 to December 2010 undergoing cardiopulmonary bypass. Three United States Food and Drug Administration-approved plasma biomarkers of cardiac stretch, N-terminal pro B-type natriuretic peptide (NTproBNP), inflammation (ST2), or fibrosis (galectin-3), were measured preoperatively and postoperatively within 6 hours of cardiac surgery. All analyses were stratified by age (<2 or ≥2 years old) to account for changing biomarker distributions during childhood and due to a significant interaction between biomarker and age for galectin-3 and NTproBNP (P <.05). Postoperatively, AKI, defined by a doubling of baseline serum creatinine, was diagnosed in 51 of 194 children <2 years and in 28 of 201 children ≥2 years. After multivariable adjustment, for children <2 years, none of the biomarkers were independently associated with AKI, whereas for children ≥2 years, the highest tertile of preoperative galectin-3 and NTproBNP as well as the postoperative galectin-3 and ST2 were associated with AKI. Preoperative plasma galectin-3 and NTproBNP and the first postoperative galectin-3 and ST2 levels were independently associated with AKI in children ≥2 years old. The performance of cardiac biomarkers after cardiac surgical procedure is affected by age, and research is required to develop biomarkers for children <2 years old. [ABSTRACT FROM AUTHOR]

Published
2021
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34. ST2 Predicts Risk of Unplanned Readmission Within 1 Year After Pediatric Congenital Heart Surgery.

Author

Parker, Devin M., Everett, Allen D., Stabler, Meagan E., Jacobs, Marshall L., Jacobs, Jeffrey P., Vricella, Luca, Thiessen-Philbrook, Heather, Parikh, Chirag R., Manlhiot, Cedric, and Brown, Jeremiah R.

Abstract

Approximately 10% to 20% of children are readmitted after congenital heart surgery. Very little is known about biomarkers as predictors of risk of unplanned readmission after pediatric congenital heart surgery. Novel cardiac biomarker ST2 may be associated with risk of unplanned readmission. ST2 concentrations are believed to reflect cardiovascular stress and fibrosis. Our objective was to explore the relationship between pre- and postoperative ST2 biomarker levels and risk of readmission within 1 year after congenital heart surgery. We prospectively enrolled pediatric patients aged < 18 years who underwent at least 1 congenital heart operation at Johns Hopkins Hospital from 2010 to 2014. Plasma samples were collected immediately before surgery and at the end of bypass. We used Kaplan-Meier survival analysis and multivariable Cox regression models to adjust for variables used in The Society of Thoracic Surgeons Congenital Heart Surgery Database mortality risk model. Of our cohort of 145 patients, we found 39 children with readmissions within 365 days. The median time to unplanned readmission was 54 days (interquartile range, 10-153). Kaplan-Meier analysis demonstrated a significant difference across terciles of pre- and postoperative ST2 biomarker levels. After adjustment, elevated serum levels of ST2 measured preoperatively and postoperatively were associated with increased risk of readmission (hazard ratio, 2.5-3.7; all P <.05). Elevated levels of ST2 are significantly associated with increased risk of unplanned readmission within 1 year after pediatric congenital heart surgery. Novel serum biomarker ST2 can be used for risk stratification or estimating postsurgical prognosis. [ABSTRACT FROM AUTHOR]

Published
2020
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37. Association of plasma-soluble ST2 and galectin-3 with cardiovascular events and mortality following cardiac surgery.

Author

Patel, Dipal M., Thiessen-Philbrook, Heather, Brown, Jeremiah R., McArthur, Eric, Moledina, Dennis G., Mansour, Sherry G., Shlipak, Michael G., Koyner, Jay L., Kavsak, Peter, Whitlock, Richard P., Everett, Allen D., Malenka, David J., Garg, Amit X., Coca, Steven G., and Parikh, Chirag R.

Abstract

Background: Cardiac surgery induces hemodynamic stress on the myocardium, and this process can be associated with significant post-operative morbidity and mortality. Soluble suppression of tumorigenicity 2 (sST2) and galectin-3 (gal-3) are biomarkers of myocardial remodeling and fibrosis; however, their potential association with post-operative changes is unknown.Methods: We measured peri-operative plasma sST2 and gal-3 levels in two prospective cohorts (TRIBE-AKI and NNE) of over 1800 patients who underwent cardiac surgery. sST2 and gal-3 levels were evaluated for association with a composite primary outcome of cardiovascular event or mortality over median follow-up periods of 3.4 and 6.0 years, respectively, for the two cohorts. Meta-analysis of hazard ratio estimates from the cohorts was performed using random effects models.Results: Cohorts demonstrated event rates of 70.2 and 66.8 per 1000 person-years for the primary composite outcome. After adjustment for clinical covariates, higher post-operative sST2 and gal-3 levels were significantly associated with cardiovascular event or mortality [pooled estimate HRs: sST2 1.29 (95% CI 1.16, 1.44); gal-3 1.26 (95% CI 1.09, 1.46)]. These associations were not significantly modified by pre-operative congestive heart failure or AKI.Conclusions: Higher post-operative sST2 and gal-3 values were associated with increased incidence of cardiovascular event or mortality. These two biomarkers should be further studied for potential clinical utility for patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

Published
2020
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38. Novel Biomarkers Improve Prediction of 365-Day Readmission After Pediatric Congenital Heart Surgery.

Author

Parker, Devin M., Everett, Allen D., Stabler, Meagan E., Vricella, Luca, Jacobs, Marshall L., Jacobs, Jeffrey P., Parikh, Chirag R., Pasquali, Sara K., and Brown, Jeremiah R.

Abstract

The purpose of this study was to evaluate the association between preoperative biomarker levels and 365-day readmission or mortality after pediatric congenital heart surgery. Children aged 18 years or younger undergoing congenital heart surgery (n = 145) at Johns Hopkins Hospital from 2010 to 2014 were enrolled in the prospective cohort. Novel biomarkers suppression of tumorgenicity 2, galectin-3, N-terminal prohormone brain natriuretic peptide, and glial fibrillary acidic protein were measured. The composite study endpoint was unplanned readmission within 365 days after discharge or mortality either in hospital during the surgical admission or within 365 days after discharge. A clinical model based on covariates used in The Society of Thoracic Surgeons Congenital Heart Surgery Database mortality risk model and an augmented model using the clinical model in conjunction with a novel biomarker panel were evaluated. Readmission or mortality within 365 days of surgery occurred among 39 pediatric patients (27%). The clinical model alone resulted in a c-statistic of 0.719 (95% confidence interval, 0.63 to 0.81). The clinical model in conjunction with the log-transformed biomarkers improved the c-statistic to 0.805 (95% confidence interval, 0.73 to 0.88). The addition of biomarkers resulted in a significant improvement to the clinical model alone (P value = 0.035). Novel biomarkers may add predictive value when assessing the likelihood of 365-day readmission or mortality after pediatric congenital heart surgery. After adjusting for clinical and novel biomarkers, preoperative and postoperative suppression of tumorgenicity 2 remained associated with 365-day readmission or mortality. Currently, The Society of Thoracic Surgeons clinical congenital mortality risk model can be applied to identify children with increased risk of repeat hospitalizations and postdischarge mortality and may inform preventative care interventions that aim to reduce these adverse events. [ABSTRACT FROM AUTHOR]

Published
2020
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39. Rationale and design of the Kidney Precision Medicine Project

Author

de Boer, Ian H., Alpers, Charles E., Azeloglu, Evren U., Balis, Ulysses G.J., Barasch, Jonathan M., Barisoni, Laura, Blank, Kristina N., Bomback, Andrew S., Brown, Keith, Dagher, Pierre C., Dighe, Ashveena L., Eadon, Michael T., El-Achkar, Tarek M., Gaut, Joseph P., Hacohen, Nir, He, Yongqun, Hodgin, Jeffrey B., Jain, Sanjay, Kellum, John A., Kiryluk, Krzysztof, Knight, Richard, Laszik, Zoltan G., Lienczewski, Chrysta, Mariani, Laura H., McClelland, Robyn L., Menez, Steven, Moledina, Dennis G., Mooney, Sean D., O’Toole, John F., Palevsky, Paul M., Parikh, Chirag R., Poggio, Emilio D., Rosas, Sylvia E., Rosengart, Matthew R., Sarwal, Minnie M., Schaub, Jennifer A., Sedor, John R., Sharma, Kumar, Steck, Becky, Toto, Robert D., Troyanskaya, Olga G., Tuttle, Katherine R., Vazquez, Miguel A., Waikar, Sushrut S., Williams, Kayleen, Wilson, Francis Perry, Zhang, Kun, Iyengar, Ravi, Kretzler, Matthias, Himmelfarb, Jonathan, Knight, Richard, Lecker, Stewart, Stillman, Isaac, Waikar, Sushrut, Mcmahon, Gearoid, Weins, Astrid, Short, Samuel, Hacohen, Nir, Hoover, Paul, Aulisio, Mark, Cooperman, Leslie, Herlitz, Leal, O’Toole, John, Poggio, Emilio, Sedor, John, Jolly, Stacey, Appelbaum, Paul, Balderes, Olivia, Barasch, Jonathan, Bomback, Andrew, Canetta, Pietro A., d’Agati, Vivette D., Kiryluk, Krzysztof, Kudose, Satoru, Mehl, Karla, Radhakrishnan, Jai, Weng, Chenhua, Barisoni, Laura, Alexandrov, Theodore, Ashkar, Tarek, Barwinska, Daria, Dagher, Pierre, Dunn, Kenneth, Eadon, Michael, Ferkowicz, Michael, Kelly, Katherine, Sutton, Timothy, Winfree, Seth, Menez, Steven, Parikh, Chirag, Rosenberg, Avi, Villalobos, Pam, Malik, Rubab, Fine, Derek, Atta, Mohammed, Monroy Trujillo, Jose Manuel, Slack, Alison, Rosas, Sylvia, Williams, Mark, Azeloglu, Evren, He, Cijang (John), Iyengar, Ravi, Hansen, Jens, Parikh, Samir, Rovin, Brad, Anderton, Chris, Pasa-Tolic, Ljiljana, Velickovic, Dusan, Lukowski, Jessica, Oliver, George (Holt), Ardayfio, Joseph, Bebiak, Jack, Brown, Keith, Campbell, Taneisha, Campbell, Catherine, Hayashi, Lynda, Jefferson, Nichole, Koewler, Robert, Roberts, Glenda, Saul, John, Shpigel, Anna, Stutzke, Edith Christine, Wright, Lorenda, Miegs, Leslie, Pinkeney, Roy, Sealfon, Rachel, Troyanskaya, Olga, Tuttle, Katherine, Dobi, Dejan, Goltsev, Yury, Lake, Blue, Zhang, Kun, Joanes, Maria, Laszik, Zoltan, Schroeder, Andrew, Sarwal, Minnie, Sigdel, Tara, Balis, Ulysses, Blanc, Victoria, He, Oliver, Hodgin, Jeffrey, Kretzler, Matthias, Mariani, Laura, Menon, Rajasree, Otto, Edgar, Schaub, Jennifer, Steck, Becky, Lienczewski, Chrysta, Eddy, Sean, Elder, Michele, Hall, Daniel, Kellum, John, Kruth, Mary, Murugan, Raghav, Palevsky, Paul, Randhawa, Parmjeet, Rosengart, Matthew, Sims-Lucas, Sunny, Stefanick, Mary, Stull, Stacy, Tublin, Mitchell, Alpers, Charles, de Boer, Ian, Dighe, Ashveena, Himmelfarb, Jonathan, Mcclelland, Robyn, Mooney, Sean, Shankland, Stuart, Williams, Kayleen, Blank, Kristina, Carson, Jonas, Dowd, Frederick, Drager, Zach, Park, Christopher, Sharma, Kumar, Zhang, Guanshi, Bansal, Shweta, Venkatachalam, Manjeri, Kermani, Asra, Lee, Simon, Lu, Christopher, Miller, Tyler, Moe, Orson, Park, Harold, Sambandam, Kamalanathan, Sanchez, Francisco, Torrealba, Jose, Robert, Toto, Vazquez, Miguel, Wang, Nancy, Gaut, Joe, Jain, Sanjay, Vijayan, Anitha, Luciano, Randy, Moledina, Dennis, Ugochukwu, Ugwuowo, Wilson, Francis Perry, and Alfano, Sandy

Abstract

Chronic kidney disease (CKD) and acute kidney injury (AKI) are common, heterogeneous, and morbid diseases. Mechanistic characterization of CKD and AKI in patients may facilitate a precision-medicine approach to prevention, diagnosis, and treatment. The Kidney Precision Medicine Project aims to ethically and safely obtain kidney biopsies from participants with CKD or AKI, create a reference kidney atlas, and characterize disease subgroups to stratify patients based on molecular features of disease, clinical characteristics, and associated outcomes. An additional aim is to identify critical cells, pathways, and targets for novel therapies and preventive strategies. This project is a multicenter prospective cohort study of adults with CKD or AKI who undergo a protocol kidney biopsy for research purposes. This investigation focuses on kidney diseases that are most prevalent and therefore substantially burden the public health, including CKD attributed to diabetes or hypertension and AKI attributed to ischemic and toxic injuries. Reference kidney tissues (for example, living-donor kidney biopsies) will also be evaluated. Traditional and digital pathology will be combined with transcriptomic, proteomic, and metabolomic analysis of the kidney tissue as well as deep clinical phenotyping for supervised and unsupervised subgroup analysis and systems biology analysis. Participants will be followed prospectively for 10 years to ascertain clinical outcomes. Cell types, locations, and functions will be characterized in health and disease in an open, searchable, online kidney tissue atlas. All data from the Kidney Precision Medicine Project will be made readily available for broad use by scientists, clinicians, and patients.

Published
2021
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40. Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19

Author

Gupta, Shruti, Wang, Wei, Hayek, Salim S., Chan, Lili, Mathews, Kusum S., Melamed, Michal L., Brenner, Samantha K., Leonberg-Yoo, Amanda, Schenck, Edward J., Radbel, Jared, Reiser, Jochen, Bansal, Anip, Srivastava, Anand, Zhou, Yan, Finkel, Diana, Green, Adam, Mallappallil, Mary, Faugno, Anthony J., Zhang, Jingjing, Velez, Juan Carlos Q., Shaefi, Shahzad, Parikh, Chirag R., Charytan, David M., Athavale, Ambarish M., Friedman, Allon N., Redfern, Roberta E., Short, Samuel A. P., Correa, Simon, Pokharel, Kapil K., Admon, Andrew J., Donnelly, John P., Gershengorn, Hayley B., Douin, David J., Semler, Matthew W., Hernán, Miguel A., and Leaf, David E.

Abstract

IMPORTANCE: Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness. OBJECTIVE: To test whether tocilizumab decreases mortality in this population. DESIGN, SETTING, AND PARTICIPANTS: The data for this study were derived from a multicenter cohort study of 4485 adults with COVID-19 admitted to participating intensive care units (ICUs) at 68 hospitals across the US from March 4 to May 10, 2020. Critically ill adults with COVID-19 were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. Data were collected retrospectively until June 12, 2020. A Cox regression model with inverse probability weighting was used to adjust for confounding. EXPOSURES: Treatment with tocilizumab in the first 2 days of ICU admission. MAIN OUTCOMES AND MEASURES: Time to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences. RESULTS: Among the 3924 patients included in the analysis (2464 male [62.8%]; median age, 62 [interquartile range {IQR}, 52-71] years), 433 (11.0%) received tocilizumab in the first 2 days of ICU admission. Patients treated with tocilizumab were younger (median age, 58 [IQR, 48-65] vs 63 [IQR, 52-72] years) and had a higher prevalence of hypoxemia on ICU admission (205 of 433 [47.3%] vs 1322 of 3491 [37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of &lt;200 mm Hg) than patients not treated with tocilizumab. After applying inverse probability weighting, baseline and severity-of-illness characteristics were well balanced between groups. A total of 1544 patients (39.3%) died, including 125 (28.9%) treated with tocilizumab and 1419 (40.6%) not treated with tocilizumab. In the primary analysis, during a median follow-up of 27 (IQR, 14-37) days, patients treated with tocilizumab had a lower risk of death compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56-0.92). The estimated 30-day mortality was 27.5% (95% CI, 21.2%-33.8%) in the tocilizumab-treated patients and 37.1% (95% CI, 35.5%-38.7%) in the non-tocilizumab–treated patients (risk difference, 9.6%; 95% CI, 3.1%-16.0%). CONCLUSIONS AND RELEVANCE: Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilizumab. However, the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed.

Published
2021
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41. The association of acute kidney injury with hospital readmission and death after pediatric cardiac surgery

Author

Nunes, Sophia, Brown, Jeremiah, Parikh, Chirag R., Greenberg, Jason H., Devarajan, Prasad, Philbrook, Heather Theissen, Pizzi, Michael, Palijan, Ana, and Zappitelli, Michael

Abstract

Acute kidney injury (AKI) in children undergoing cardiac surgery (CS) is strongly associated with increased hospital mortality and length of stay. The association of AKI with postdischarge outcomes is unclear. We evaluated the association of AKI with all-cause readmissions and death within 30 days and 1 year of CS discharge.

Published
2020
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42. Kidney nonprocurement in solid organ donors in the United States

Author

Yu, Kathleen, King, Kristen, Husain, Syed A., Dube, Geoffrey K., Stevens, Jacob S., Ratner, Lloyd E., Cooper, Matthew, Parikh, Chirag R., and Mohan, Sumit

Abstract

There are limited data on the nonprocurement of kidneys from solid organ donors. Analysis of Standard Transplant Analysis and Research files was undertaken on all deceased donors in the United States with at least 1 solid organ recovered. From 2000 to 2018, 21 731 deceased donor kidneys (averaging 1144 kidneys per year) were not procured. No kidneys were procured from 8% of liver donors, 3% of heart donors, and 3% of lung donors. Compared to donors with all kidneys procured, those with none procured were older and more likely obese, black, hypertensive, diabetic, hepatitis C positive, smokers, Public Health Service – Increased Risk designated, deceased after cardiac death, or deceased after cerebrovascular accident. Although these donors had lower quality kidneys (median Kidney Donor Risk Index (interquartile range) 1.9 (1.0) vs 1.2 (0.7)), there was substantial overlap in quality between nonprocured and procured kidneys. Nearly one third of nonprocurements were attributed to donor history. Donors with elevated terminal creatinine likely resulting from acute kidney injury (AKI) had higher odds of kidney nonprocurement. Nonprocurement odds varied widely across Organ Procurement and Transplantation Network regions, with a positive correlation between donor kidney nonprocurements and kidney discards at the donation service area level. These findings suggest current discard rates underestimate the underutilization of deceased donor kidneys and more research is needed to optimize safe procurement and utilization of kidneys from donors with AKI. In this analysis of deceased donors in the United States between 2000–2018, the authors show that kidney nonprocurement, despite procurement of a lung, heart, or liver, was associated with donor history and elevated terminal creatinine that likely reflect donor acute kidney injury.

Published
2020
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43. Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US

Author

Gupta, Shruti, Hayek, Salim S., Wang, Wei, Chan, Lili, Mathews, Kusum S., Melamed, Michal L., Brenner, Samantha K., Leonberg-Yoo, Amanda, Schenck, Edward J., Radbel, Jared, Reiser, Jochen, Bansal, Anip, Srivastava, Anand, Zhou, Yan, Sutherland, Anne, Green, Adam, Shehata, Alexandre M., Goyal, Nitender, Vijayan, Anitha, Velez, Juan Carlos Q., Shaefi, Shahzad, Parikh, Chirag R., Arunthamakun, Justin, Athavale, Ambarish M., Friedman, Allon N., Short, Samuel A. P., Kibbelaar, Zoe A., Abu Omar, Samah, Admon, Andrew J., Donnelly, John P., Gershengorn, Hayley B., Hernán, Miguel A., Semler, Matthew W., and Leaf, David E.

Abstract

IMPORTANCE: The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical illness from COVID-19. OBJECTIVES: To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020. EXPOSURES: Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds. MAIN OUTCOMES AND MEASURES: The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes. RESULTS: A total of 2215 patients (mean [SD] age, 60.5 [14.5] years; 1436 [64.8%] male; 1738 [78.5%] with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (≥80 vs &lt;40 years of age: odds ratio [OR], 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (≥40 vs &lt;25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (Pao2:Fio2&lt;100 vs ≥300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2-4 vs 0: OR, 2.61; 95% CI, 1.30–5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46–4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (&lt;50 vs ≥100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies. CONCLUSIONS AND RELEVANCE: This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.

Published
2020
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44. Early Prediction of Acute Kidney Injury in the Emergency Department With Machine-Learning Methods Applied to Electronic Health Record Data

Author

Martinez, Diego A., Levin, Scott R., Klein, Eili Y., Parikh, Chirag R., Menez, Steven, Taylor, Richard A., and Hinson, Jeremiah S.

Abstract

Acute kidney injury occurs commonly and is a leading cause of prolonged hospitalization, development and progression of chronic kidney disease, and death. Early acute kidney injury treatment can improve outcomes. However, current decision support is not able to detect patients at the highest risk of developing acute kidney injury. We analyzed routinely collected emergency department (ED) data and developed prediction models with capacity for early identification of ED patients at high risk for acute kidney injury.

Published
2020
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45. A Review of Donor Acute Kidney Injury and Posttransplant Outcomes

Author

Koyawala, Neel and Parikh, Chirag R.

Abstract

Although over 90 000 people are on the kidney transplant waitlist in the United States, some kidneys that are viable for transplantation are discarded. Transplant surgeons are more likely to discard deceased donors with acute kidney injury (AKI) versus without AKI (30% versus 18%). AKI is defined using changes in creatinine from baseline. Transplant surgeons can use DonorNet data, including admission, peak, and terminal serum creatinine, and biopsy data when available to differentiate kidneys with AKI from those with chronic injury. Although chronic kidney disease is associated with reduced graft survival, an abundance of literature has demonstrated similar graft survival for deceased donors with AKI versus donors without AKI. Donors with AKI are more likely to undergo delayed graft function but have similar long-term outcomes as donors without AKI. The mechanism for similar graft survival is unclear. Some hypothesized mechanisms include (1) ischemic preconditioning; (2) posttransplant and host factors playing a greater role in long-term survival than donor factors; and (3) selection bias of transplanting only relatively healthy donor kidneys with AKI. Existing literature suggests transplanting more donor kidneys with stage 1 and 2 AKI, and cautious utilization of stage 3 AKI donors, may increase the pool of viable kidneys. Doing so can reduce the number of people who die on the waitlist by over 500 every year.

Published
2020
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46. Urine Injury Biomarkers Are Not Associated With Kidney Transplant Failure

Author

Koyawala, Neel, Reese, Peter P., Hall, Isaac E., Jia, Yaqi, Thiessen-Philbrook, Heather R., Mansour, Sherry G., Doshi, Mona D., Akalin, Enver, Bromberg, Jonathan S., Harhay, Meera N., Mohan, Sumit, Muthukumar, Thangamani, Schröppel, Bernd, Singh, Pooja, Weng, Francis L., and Parikh, Chirag R.

Abstract

Supplemental Digital Content is available in the text.

Published
2020
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47. Outcomes From Right Versus Left Deceased-Donor Kidney Transplants: A US National Cohort Study

Author

Kulkarni, Sanjay, Wei, Guo, Jiang, Wei, Lopez, Licia A., Parikh, Chirag R., and Hall, Isaac E.

Abstract

There may be important transplant-related differences between right and left kidneys, including logistical/surgical considerations about vessel length for the right compared to the left kidney from the same donor. Because US centers choose between the right and left kidney when their recipient is ranked higher on a “match-run,” we sought to determine whether deceased-donor right kidneys have had worse posttransplantation outcomes than left kidneys.

Published
2020
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48. Post–Acute Kidney Injury Proteinuria and Subsequent Kidney Disease Progression: The Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study

Author

Hsu, Chi-yuan, Chinchilli, Vernon M., Coca, Steven, Devarajan, Prasad, Ghahramani, Nasrollah, Go, Alan S., Hsu, Raymond K., Ikizler, T. Alp, Kaufman, James, Liu, Kathleen D., Parikh, Chirag R., Reeves, W. Brian, Wurfel, Mark, Zappitelli, Michael, Kimmel, Paul L., and Siew, Edward D.

Abstract

IMPORTANCE: Among patients who had acute kidney injury (AKI) during hospitalization, there is a need to improve risk prediction such that those at highest risk for subsequent loss of kidney function are identified for appropriate follow-up. OBJECTIVE: To evaluate the association of post-AKI proteinuria with increased risk of future loss of renal function. DESIGN, SETTING, AND PARTICIPANTS: The Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study was a multicenter prospective cohort study including 4 clinical centers in North America included 1538 patients enrolled 3 months after hospital discharge between December 2009 and February 2015. EXPOSURES: Urine albumin-to-creatinine ratio (ACR) quantified 3 months after hospital discharge. MAIN OUTCOMES AND MEASURES: Kidney disease progression defined as halving of estimated glomerular filtration rate (eGFR) or end-stage renal disease. RESULTS: Of the 1538 participants, 769 (50%) had AKI durring hospitalization. The baseline study visit took place at a mean (SD) 91 (23) days after discharge. The mean (SD) age was 65 (13) years; the median eGFR was 68 mL/min/1.73 m2; and the median urine ACR was 15 mg/g. Overall, 547 (37%) study participants were women and 195 (13%) were black. After a median follow-up of 4.7 years, 138 (9%) participants had kidney disease progression. Higher post-AKI urine ACR level was associated with increased risk of kidney disease progression (hazard ratio [HR], 1.53 for each doubling; 95% CI, 1.45-1.62), and urine ACR measurement was a strong discriminator for future kidney disease progression (C statistic, 0.82). The performance of urine ACR was stronger in patients who had had AKI than in those who had not (C statistic, 0.70). A comprehensive model of clinical risk factors (eGFR, blood pressure, and demographics) including ACR provided better discrimination for predicting kidney disease progression after hospital discharge among those who had had AKI (C statistic, 0.85) vs those who had not (C statistic, 0.76). In the entire matched cohort, after taking into account urine ACR, eGFR, demographics, and traditional chronic kidney risk factors determined 3 months after discharge, AKI (HR, 1.46; 95% CI, 0.51-4.13 for AKI vs non-AKI) or severity of AKI (HR, 1.54; 95% CI, 0.50-4.72 for AKI stage 1 vs non-AKI; HR, 0.56; 95% CI, 0.07-4.84 for AKI stage 2 vs non-AKI; HR, 2.24; 95% CI, 0.33-15.29 for AKI stage 3 vs non-AKI) was not independently associated with more rapid kidney disease progression. CONCLUSIONS AND RELEVANCE: Proteinuria level is a valuable risk-stratification tool in the post-AKI period. These results suggest there should be more widespread and routine quantification of proteinuria after hospitalized AKI.

Published
2020
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49. Kidney Biomarkers of Injury and Repair as Predictors of Contrast-Associated AKI: A Substudy of the PRESERVE Trial

Author

Parikh, Chirag R., Liu, Caroline, Mor, Maria K., Palevsky, Paul M., Kaufman, James S., Thiessen Philbrook, Heather, and Weisbord, Steven D.

Abstract

The PRESERVE trial used a 2 × 2 factorial design to compare intravenous saline solution with intravenous sodium bicarbonate solution and oral N-acetylcysteine with placebo for the prevention of 90-day major adverse kidney events and death (MAKE-D) and contrast-associated acute kidney injury (CA-AKI) among patients with chronic kidney disease undergoing angiography. In this ancillary study, we evaluated the predictive capacities of preangiography injury and repair proteins in urine and plasma for MAKE-D, CA-AKI, and their impact on trial design.

Published
2020
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