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2. The Microbiome and Protein Carbamylation: Potential Targets for Protein-Restricted Diets Supplemented with Ketoanalogues in Predialysis Chronic Kidney Disease.

Author

Faerber, Valentin, Kuhn, Katharina, Garneata, Liliana, Kalim, Sahir, Raj, Dominic, Westphal, Martin, and Kalantar-Zadeh, Kamyar

Subjects
carbamylation, chronic kidney disease, diet, dysbiosis, microbiome, posttranslational protein modification, protein restricted, urea, uremic toxin, Humans, Protein Carbamylation, Diet, Protein-Restricted, Dysbiosis, Quality of Life, Uremic Toxins, Renal Dialysis, Microbiota, Dietary Supplements, Disease Progression
Abstract

In chronic kidney disease (CKD), metabolic derangements resulting from the interplay between decreasing renal excretory capacity and impaired gut function contribute to accelerating disease progression and enhancing the risk of complications. To protect residual kidney function and improve quality of life in conservatively managed predialysis CKD patients, current guidelines recommend protein-restricted diets supplemented with essential amino acids (EAAs) and their ketoanalogues (KAs). In clinical studies, such an approach improved nitrogen balance and other secondary metabolic disturbances, translating to clinical benefits, mainly the delayed initiation of dialysis. There is also increasing evidence that a protein-restricted diet supplemented with KAs slows down disease progression. In the present review article, recent insights into the role of KA/EAA-supplemented protein-restricted diets in delaying CKD progression are summarized, and possible mechanistic underpinnings, such as protein carbamylation and gut dysbiosis, are elucidated. Emerging evidence suggests that lowering urea levels may reduce protein carbamylation, which might contribute to decreased morbidity and mortality. Protein restriction, alone or in combination with KA/EAA supplementation, modulates gut dysbiosis and decreases the generation of gut-derived uremic toxins associated, e.g., with cardiovascular disease, inflammation, protein energy wasting, and disease progression. Future studies are warranted to assess the effects on the gut microbiome, the generation of uremic toxins, as well as markers of carbamylation.

Published
2023

9. Metabolites Associated With Uremic Symptoms in Patients With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Author

Dember, Laura M., Landis, J. Richard, Townsend, Raymond R., Appel, Lawrence, Fink, Jeffrey, Rahman, Mahboob, Horwitz, Edward J., Taliercio, Jonathan J., Rao, Panduranga, Sondheimer, James H., Lash, James P., Chen, Jing, Go, Alan S., Parsa, Afshin, Rankin, Tracy, Wulczyn, Kendra E., Shafi, Tariq, Anderson, Amanda, Rincon-Choles, Hernan, Clish, Clary B., Denburg, Michelle, Feldman, Harold I., He, Jiang, Hsu, Chi-yuan, Kelly, Tanika, Kimmel, Paul L., Mehta, Rupal, Nelson, Robert G., Ramachandran, Vasan, Ricardo, Ana, Shah, Vallabh O., Srivastava, Anand, Xie, Dawei, Rhee, Eugene P., and Kalim, Sahir

Published
2024
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12. The design and baseline characteristics for the HOPE Consortium Trial to reduce pain and opioid use in hemodialysis

Author

Dember, Laura M., Hsu, Jesse Y., Bernardo, Leah, Cavanaugh, Kerri L., Charytan, David M., Crowley, Susan T., Cukor, Daniel, Doorenbos, Ardith Z., Edwards, David A., Esserman, Denise, Fischer, Michael J., Jhamb, Manisha, Joffe, Steven, Johansen, Kirsten L., Kalim, Sahir, Keefe, Francis J., Kimmel, Paul L., Krebs, Erin E., Kuzla, Natalie, Mehrotra, Rajnish, Mishra, Puneet, Pellegrino, Bethany, Steel, Jennifer L., Unruh, Mark L., White, David M., Yabes, Jonathan G., and Becker, William C.

Published
2024
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18. Metabolites Associated With Uremic Symptoms in Patients With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Author

Wulczyn, Kendra E., primary, Shafi, Tariq, additional, Anderson, Amanda, additional, Rincon-Choles, Hernan, additional, Clish, Clary B., additional, Denburg, Michelle, additional, Feldman, Harold I., additional, He, Jiang, additional, Hsu, Chi-yuan, additional, Kelly, Tanika, additional, Kimmel, Paul L., additional, Mehta, Rupal, additional, Nelson, Robert G., additional, Ramachandran, Vasan, additional, Ricardo, Ana, additional, Shah, Vallabh O., additional, Srivastava, Anand, additional, Xie, Dawei, additional, Rhee, Eugene P., additional, Kalim, Sahir, additional, Dember, Laura M., additional, Landis, J. Richard, additional, Townsend, Raymond R., additional, Appel, Lawrence, additional, Fink, Jeffrey, additional, Rahman, Mahboob, additional, Horwitz, Edward J., additional, Taliercio, Jonathan J., additional, Rao, Panduranga, additional, Sondheimer, James H., additional, Lash, James P., additional, Chen, Jing, additional, Go, Alan S., additional, Parsa, Afshin, additional, and Rankin, Tracy, additional

Published
2024
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19. The design and baseline characteristics for the HOPE Consortium Trial to reduce pain and opioid use in hemodialysis

Author

Dember, Laura M., primary, Hsu, Jesse Y., additional, Bernardo, Leah, additional, Cavanaugh, Kerri L., additional, Charytan, David M., additional, Crowley, Susan T., additional, Cukor, Daniel, additional, Doorenbos, Ardith Z., additional, Edwards, David A., additional, Esserman, Denise, additional, Fischer, Michael J., additional, Jhamb, Manisha, additional, Joffe, Steven, additional, Johansen, Kirsten L., additional, Kalim, Sahir, additional, Keefe, Francis J., additional, Kimmel, Paul L., additional, Krebs, Erin E., additional, Kuzla, Natalie, additional, Mehrotra, Rajnish, additional, Mishra, Puneet, additional, Pellegrino, Bethany, additional, Steel, Jennifer L., additional, Unruh, Mark L., additional, White, David M., additional, Yabes, Jonathan G., additional, and Becker, William C., additional

Published
2023
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21. Proinflammatory P2Y14 receptor inhibition protects against ischemic acute kidney injury in mice

Author

Battistone, Maria Agustina, Mendelsohn, Alexandra C., Spallanzani, Raul German, Allegretti, Andrew S., Liberman, Rachel N., Sesma, Juliana, Kalim, Sahir, Wall, Susan M., Bonventre, Joseph V., Lazarowski, Eduardo R., Brown, Dennis, and Breton, Sylvie

Subjects
Glucose, Cardiac patients, Kidney diseases -- Prevention, Health care industry
Abstract

Ischemic acute kidney injury (AKI), a complication that frequently occurs in hospital settings, is often associated with hemodynamic compromise, sepsis, cardiac surgery, or exposure to nephrotoxins. Here, using a murine renal ischemia/ reperfusion injury (IRI) model, we show that intercalated cells (ICs) rapidly adopted a proinflammatory phenotype after IRI. Wwe demonstrate that during the early phase of AKI either blockade of the proinflammatory P2Y14 receptor located on the apical membrane of ICs or ablation of the gene encoding the P2Y14 receptor in ICs (a) inhibited IRI-induced increase of chemokine expression in ICs, (b) reduced neutrophil and monocyte renal infiltration, (c) reduced the extent of kidney dysfunction, and (d) attenuated proximal tubule damage. These observations indicate that the P2Y14 receptor participates in the very first inflammatory steps associated with ischemic AKI. In addition, we show that the concentration of the P2Y14 receptor ligand UDP-glucose (UDP-Glc) was higher in urine samples from intensive care unit patients who developed AKI compared with patients without AKI. In particular, we observed a strong correlation between UDP-Glc concentration and the development of AKI in cardiac surgery patients. Our study identifies the UDP-Glc/P2Y14 receptor axis as a potential target for the prevention and/or attenuation of ischemic AKI., Introduction Acute kidney injury (AKI) is a frequent medical complication seen in hospitalized patients. It is associated with an increased length of hospital stay, the development of chronic kidney disease, [...]

Published
2020
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24. Severe Hyponatremia Correction, Mortality, and Central Pontine Myelinolysis

Author

Seethapathy, Harish, primary, Zhao, Sophia, additional, Ouyang, Tianqi, additional, Passos, Christie, additional, Sarang, Adviti, additional, Cheung, Pui W., additional, Waikar, Sushrut S., additional, Steele, David J.R., additional, Kalim, Sahir, additional, Allegretti, Andrew S., additional, Ayus, Juan Carlos, additional, and Nigwekar, Sagar U., additional

Published
2023
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27. A Plasma Long‐Chain Acylcarnitine Predicts Cardiovascular Mortality in Incident Dialysis Patients

Author

Kalim, Sahir, Clish, Clary B, Wenger, Julia, Elmariah, Sammy, Yeh, Robert W, Deferio, Joseph J, Pierce, Kerry, Deik, Amy, Gerszten, Robert E, Thadhani, Ravi, and Rhee, Eugene P

Subjects
Cardiovascular, Clinical Research, Kidney Disease, Good Health and Well Being, Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Carnitine, Case-Control Studies, Chi-Square Distribution, Chromatography, Liquid, Female, Humans, Kidney Failure, Chronic, Logistic Models, Male, Mass Spectrometry, Metabolomics, Middle Aged, Multivariate Analysis, Odds Ratio, Prospective Studies, Renal Dialysis, Risk Factors, Time Factors, Treatment Outcome, Uremia, cardiovascular disease, dialysis, metabolism, mortality, risk factors, Cardiorespiratory Medicine and Haematology
Abstract

BackgroundThe marked excess in cardiovascular mortality that results from uremia remains poorly understood.Methods and resultsIn 2 independent, nested case-control studies, we applied liquid chromatography-mass spectrometry-based metabolite profiling to plasma obtained from participants of a large cohort of incident hemodialysis patients. First, 100 individuals who died of a cardiovascular cause within 1 year of initiating hemodialysis (cases) were randomly selected along with 100 individuals who survived for at least 1 year (controls), matched for age, sex, and race. Four highly intercorrelated long-chain acylcarnitines achieved the significance threshold adjusted for multiple testing (P

Published
2013

30. Intravenous Sodium Thiosulphate for Calciphylaxis of Chronic Kidney Disease

Author

Wen, Wen, primary, Portales-Castillo, Ignacio, additional, Seethapathy, Rituvanthikaa, additional, Durant, Olivia, additional, Mengesha, Beza, additional, Krinsky, Scott, additional, Kroshinsky, Daniela, additional, Kalim, Sahir, additional, Goverman, Jeremy, additional, Nazarian, Rosalynn M., additional, Chitalia, Vipul, additional, Malhotra, Rajeev, additional, Kramann, Rafael, additional, Malhotra, Cindy K., additional, and Nigwekar, Sagar U., additional

Published
2023
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31. Intravenous Sodium Thiosulphate for Calciphylaxis of Chronic Kidney Disease:A Systematic Review and Meta-analysis

Author

Wen, Wen, Portales-Castillo, Ignacio, Seethapathy, Rituvanthikaa, Durant, Olivia, Mengesha, Beza, Krinsky, Scott, Kroshinsky, Daniela, Kalim, Sahir, Goverman, Jeremy, Nazarian, Rosalynn M., Chitalia, Vipul, Malhotra, Rajeev, Kramann, Rafael, Malhotra, Cindy K., Nigwekar, Sagar U., Wen, Wen, Portales-Castillo, Ignacio, Seethapathy, Rituvanthikaa, Durant, Olivia, Mengesha, Beza, Krinsky, Scott, Kroshinsky, Daniela, Kalim, Sahir, Goverman, Jeremy, Nazarian, Rosalynn M., Chitalia, Vipul, Malhotra, Rajeev, Kramann, Rafael, Malhotra, Cindy K., and Nigwekar, Sagar U.

Abstract

Importance: Calciphylaxis is a rare disease with high mortality mainly involving patients with chronic kidney disease (CKD). Sodium thiosulphate (STS) has been used as an off-label therapeutic in calciphylaxis, but there is a lack of clinical trials and studies that demonstrate its effect compared with those without STS treatment. Objective: To perform a meta-analysis of the cohort studies that provided data comparing outcomes among patients with calciphylaxis treated with and without intravenous STS. Data Sources: PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched using relevant terms and synonyms including sodium thiosulphate and calci∗ without language restriction. Study Selection: The initial search was for cohort studies published before August 31, 2021, that included adult patients diagnosed with CKD experiencing calciphylaxis and could provide a comparison between patients treated with and without intravenous STS. Studies were excluded if they reported outcomes only from nonintravenous administration of STS or if the outcomes for CKD patients were not provided. Data Extraction and Synthesis: Random-effects models were performed. The Egger test was used to measure publication bias. Heterogeneity was assessed using the I2test. Main Outcomes and Measures: Skin lesion improvement and survival, synthesized as ratio data by a random-effects empirical Bayes model. Results: Among the 5601 publications retrieved from the targeted databases, 19 retrospective cohort studies including 422 patients (mean age, 57 years; 37.3% male) met the eligibility criteria. No difference was observed in skin lesion improvement (12 studies with 110 patients; risk ratio, 1.23; 95% CI, 0.85-1.78) between the STS and the comparator groups. No difference was noted for the risk of death (15 studies with 158 patients; risk ratio, 0.88; 95% CI, 0.70-1.10) and overall survival using time-to-event data (3 studies with 269 participants; hazard rat

Published
2023

41. Metabolite profiling of CKD progression in the chronic renal insufficiency cohort study

Author

Wen, Donghai, primary, Zheng, Zihe, additional, Surapaneni, Aditya, additional, Yu, Bing, additional, Zhou, Linda, additional, Zhou, Wen, additional, Xie, Dawei, additional, Shou, Haochang, additional, Avila-Pacheco, Julian, additional, Kalim, Sahir, additional, He, Jiang, additional, Hsu, Chi-Yuan, additional, Parsa, Afshin, additional, Rao, Panduranga, additional, Sondheimer, James, additional, Townsend, Raymond, additional, Waikar, Sushrut S., additional, Rebholz, Casey M., additional, Denburg, Michelle R., additional, Kimmel, Paul L., additional, Vasan, Ramachandran S., additional, Clish, Clary B., additional, Coresh, Josef, additional, Feldman, Harold I., additional, Grams, Morgan E., additional, and Rhee, Eugene P., additional

Published
2022
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43. FGF23 and Cardiovascular Structure and Function in Advanced Chronic Kidney Disease

Author

Halim, Arvin, primary, Burney, Heather N., additional, Li, Xiaochun, additional, Li, Yang, additional, Tomkins, Claudia, additional, Siedlecki, Andrew M., additional, Lu, Tzong-shi, additional, Kalim, Sahir, additional, Thadhani, Ravi, additional, Moe, Sharon, additional, Ting, Stephen M.S., additional, Zehnder, Daniel, additional, Hiemstra, Thomas F., additional, and Lim, Kenneth, additional

Published
2022
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46. List of Contributors

Author

Adler, Gail K., primary, Ananth Karumanchi, S., additional, Ayoob, Rose, additional, Ayus, Juan C., additional, Bakris, George, additional, Baudrand, Rene, additional, Berl, Tomas, additional, Bollag, Wendy B., additional, Brines, Michael, additional, Brown, Alex J., additional, Brown, Ronald B., additional, Burnett Jr., John C., additional, Carey, Robert M., additional, Catanzaro, Daniel F., additional, Chauhan, Veeraish, additional, Chen, Yang, additional, Dusso, Adriana S., additional, Ecelbarger, Carolyn M., additional, Ferrario, Carlos M., additional, Friedman, Peter A., additional, Garg, Rajesh, additional, Gomez-Sanchez, Celso E., additional, Gomez-Sanchez, Elise P., additional, Gotoh, Koro, additional, Isales, Carlos M., additional, Kalim, Sahir, additional, Ko, Benjamin, additional, Kraut, Jeffrey A., additional, Macdougall, Iain C., additional, Mahan, John D., additional, Meems, Laura, additional, Menard, Joel, additional, Mihailidou, Anastasia S., additional, Mole, David R., additional, Monticone, Silvia, additional, Moritz, Michael L., additional, Nagami, Glenn T., additional, Nigwekar, Sagar U., additional, Padia, Shetal H., additional, Palmer, Biff F., additional, Parashar, Akhil, additional, Pojoga, Luminita, additional, Rainey, William E., additional, Ratcliffe, Peter J., additional, Razzaque, Mohammed S., additional, Rhee, Connie M., additional, Romero, Jose R., additional, Sands, Jeff M., additional, Schlanger, Lynn E., additional, Schrier, Robert W., additional, Shibata, Hirotaka, additional, Sica, Domenic A., additional, Simonson, Donald C., additional, Singh, Ajay K., additional, Sud, Karan, additional, Tiwari, Swasti, additional, Trask, Aaron J., additional, and Vilardaga, Jean-Pierre, additional

Published
2017
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48. Intravenous sodium thiosulphate for vascular calcification of hemodialysis patients—a systematic review and meta-analysis

Author

Wen, Wen, primary, Portales-Castillo, Ignacio, additional, Seethapathy, Rituvanthikaa, additional, Krinsky, Scott, additional, Kroshinsky, Daniela, additional, Kalim, Sahir, additional, Goverman, Jeremy, additional, Nazarian, Rosalynn M, additional, Chitalia, Vipul, additional, Malhotra, Rajeev, additional, Kramann, Rafael, additional, Malhotra, Cindy K, additional, and Nigwekar, Sagar U, additional

Published
2022
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49. Calciphylaxis is Associated with Pyrophosphate Deficiency in Dialysis Patient's Exploratory Study

Author

Nigwekar, Sagar, primary, St. Hillien, Shelsea, additional, Seethapathy, Ritu, additional, Krinsky, Scott, additional, Torcatti, Jeanfranco, additional, Howe, Jennifer, additional, Kalim, Sahir, additional, Portales-Castillo, Ignacio, additional, Mengesha, Beza, additional, Cizman, Borut, additional, Sabbagh, Yves, additional, and Wen, Wen, additional

Published
2022
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50. MO751: Calciphylaxis is Characterized by Pyrophosphate Deficiency in Dialysis Patients: A Pilot Study

Author

Nigwekar, Sagar, primary, St Hillien, Shelsea, additional, Seethapathy, Rituvanthikaa, additional, Krinsky, Scott, additional, Torcatti, Jeanfranco, additional, Howe, Jennifer, additional, Kalim, Sahir, additional, Portales-Castillo, Ignacio, additional, Mengesha, Beza, additional, Wen, Wen, additional, Cizman, Borut, additional, and Sabbagh, Yves, additional

Published
2022
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