Article
Physiology
Peder Berg, Samuel L. Svendsen, Thi Thuy Linh Hoang, Helle A. Praetorius, Mads V. Sorensen, Jens Leipziger
Summary: Patients with cystic fibrosis have an increased risk of developing metabolic alkalosis due to altered renal HCO3- handling. This study found that CFTR KO mice develop metabolic alkalosis during a chronic base-load because they are unable to sufficiently elevate renal HCO3- excretion, likely due to markedly reduced pendrin function in the absence of CFTR.
Article
Veterinary Sciences
Takamasa Itoi, Natsuki Akashi, Yuki Shimizu, Keisuke Sugimoto, Akihisa Hata, Kenji Kutara, Takako Shimokawa Miyama, Teppei Kanda
Summary: This study reports the first case of zonisamide-associated renal tubular acidosis in a golden retriever. The dog showed adverse effects of zonisamide and was diagnosed with distal renal tubular acidosis. Treatment with bicarbonate was effective in alleviating the symptoms.
VETERINARY MEDICINE AND SCIENCE
(2022)
Article
Multidisciplinary Sciences
Qing Zhang, Liyan Jian, Deqiang Yao, Bing Rao, Ying Xia, Kexin Hu, Shaobai Li, Yafeng Shen, Mi Cao, An Qin, Jie Zhao, Yu Cao
Summary: Cells maintain a narrow physiological pH by exchanging intracellular bicarbonate for extracellular chloride. The cryo-EM structures of human anion exchanger 2 (AE2) in five major operating states and one transitional state were determined, collectively demonstrating the process of pH-balancing. Critical structural features were identified, revealing an interlock mechanism for interactions among different domains of AE2 and the self-inhibitory effect of a loop structure. These findings provide insights into the dynamic process of anion exchange across membranes and the pH-sensitive pH-rebalancing activity of AE2.
NATURE COMMUNICATIONS
(2023)
Article
Gastroenterology & Hepatology
Floris J. M. Roos, Marcel J. C. Bijvelds, Monique M. A. Verstegen, Henk P. Roest, Herold J. Metselaar, Wojciech G. Polak, Hugo R. de Jonge, Jan N. M. IJzermans, Luc J. W. van der Laan
Summary: This study investigated the effect of hypoxia on CFTR activity in intrahepatic cholangiocyte organoids (ICOs) and tested drug interventions to restore bicarbonate secretion. The results showed that hypoxia significantly decreased CFTR activity and increased cell susceptibility to bile toxicity.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Xin Hui, Dan Zhang, Chunying Wu, Yifan Ma, Huihui Zhou, Yunbo Zhu
Summary: Green organic synthesis mediated by visible-light chemistry using water as a medium has been reported. A water-phase electron donor-acceptor (WEDA) platform has been developed, allowing for the synthesis of sterically hindered tertiary alcohols with quaternary sp(3)-carbon centers in a green chemistry approach. The method has also been applied for the late-stage functionalization of several commercially available pharmaceutical compounds.
Article
Multidisciplinary Sciences
Arnold Piek, Leonie Smit, Navin Suthahar, Stephan J. L. Bakker, Rudolf A. de Boer, Herman H. W. Sillje
Summary: Plasma levels of DKK3 are associated with cardiovascular risk factors, but are generally not independently associated with prevalent and new-onset CVD and CKD, and only predicted for new-onset CKD in those subjects with the lowest UAE values.
SCIENTIFIC REPORTS
(2021)
Article
Nutrition & Dietetics
Alisson Diego Machado, Dirce Maria Marchioni, Paulo Andrade Lotufo, Isabela Martins Bensenor, Silvia Maria Titan
Summary: The study evaluated the association between dietary acid load (DAL) and the risk of mortality and kidney replacement therapy (KRT) in patients with chronic kidney disease (CKD). The results showed that NEAP and PRAL were positively associated with the risk of KRT, but not with all-cause mortality.
EUROPEAN JOURNAL OF CLINICAL NUTRITION
(2023)
Article
Health Care Sciences & Services
Fabiana Ciciriello, Marcel J. C. Bijvelds, Federico Alghisi, Kelly F. Meijsen, Luca Cristiani, Claudio Sorio, Paola Melotti, Alessandro G. Fiocchi, Vincenzina Lucidi, Hugo R. De Jonge
Summary: This study evaluated the effect of ELX/TEZ/IVA on rare CFTR variants using organoid cultures and measured CFTR-mediated electrical current. The results showed that ELX/TEZ/IVA significantly enhanced CFTR function and improved clinical biomarkers in patients. The study also proposed that this functional CFTR assay may guide personalized medicine.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Zhi Wei Zeng, Paul Linsdell, Regis Pomes
Summary: The recent atomistic structures of the CFTR Cl- channel provide insights into the molecular understanding of cystic fibrosis. Molecular dynamics simulations show that under a strong electric field, the protein spontaneously transitions from a closed state to an open state, allowing Cl- ions to translocate through the narrow pore bottleneck. The observed pathway of Cl- ions is consistent with the locations of mutations that affect CFTR channel function.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Endocrinology & Metabolism
Sanna Laurila, Eleni Rebelos, Minna Lahesmaa, Lihua Sun, Katharina Schnabl, Tia-Mari Peltomaa, Riku Klen, Mueez U-Din, Miikka-Juhani Honka, Olli Eskola, Anna K. Kirjavainen, Lauri Nummenmaa, Martin Klingenspor, Kirsi A. Virtanen, Pirjo Nuutila
Summary: The study investigated the effects of the gastrointestinal hormone secretin on the myocardium and kidneys. The results showed that secretin increased myocardial glucose uptake and renal clearance, demonstrating its potential as a drug candidate for heart and kidney failure studies.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Pharmacology & Pharmacy
Jia Liu, Allison P. Berg, Yiting Wang, Walailak Jantarajit, Katy J. Sutcliffe, Edward B. Stevens, Lishuang Cao, Marko J. Pregel, David N. Sheppard
Summary: This study investigates the action of a new CFTR potentiator, CP-628006, and compares it with the marketed CFTR potentiator ivacaftor. CP-628006 has distinct effects compared to ivacaftor, suggesting a different mechanism of CFTR potentiation. The emergence of CFTR potentiators with diverse modes of action makes therapy with combinations of potentiators a possibility.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Medical Laboratory Technology
Alfredo G. Casanova, Isabel Fuentes-Calvo, Maria T. Hernandez-Sanchez, Miguel Quintero, Paula Toral, Maria T. Caballero, Carlos Martinez-Salgado, Ana Morales, Anita T. Layton, Nelida Eleno, Francisco J. Lopez-Hernandez
Summary: Diagnosis of AKI relies on plasma creatinine concentration but also requires detection of alterations in other aspects of renal function. The furosemide stress test has been validated in rats for detecting subclinical tubular alterations. Impaired response to the FST was observed in predisposed rats with AKI.
TRANSLATIONAL RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Wei Chen, Bing Wang, Shanshan Liang, Meng Wang, Lingna Zheng, Si Xu, Jiali Wang, Hao Fang, Pu Yang, Weiyue Feng
Summary: This study reveals that graphene oxide nanosheets are excreted in urine through the kidneys, but the lateral size of the nanosheets affects their distribution in the kidneys and kidney injury. Small nanosheets are mainly excreted via glomerular filtration, while large nanosheets are predominantly excreted via proximal tubular secretion. During renal elimination, high-dose nanosheet treatment can induce different kidney injuries, with small nanosheets causing glomerular damage and large nanosheets causing tubular damage.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Article
Chemistry, Physical
Rhys D. Barker, Yuqi Yu, Leonardo De Maria, Linus O. Johannissen, Nigel S. Scrutton
Summary: In order to rationally engineer flavin-dependent halogenases (FDHs), it is important to understand the reaction mechanism and substrate interactions in the active site. This study presents the most likely mechanism for halogenation based on molecular dynamics simulations and density functional theory cluster models of FDH PrnA.
Article
Agriculture, Multidisciplinary
Bendong Yang, Meiling Xin, Shufei Liang, Yuhong Huang, Jingda Li, Chao Wang, Chao Liu, Xinhua Song, Jinyue Sun, Wenlong Sun
Summary: Naringenin reduces hyperuricemia and renal inflammation by promoting uric acid excretion and attenuating the release of inflammatory cytokines.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Physiology
Samuel L. Svendsen, Simon Kornvig, Peder Berg, Iben S. Jensen, Isabela B. B. A. de Araujo, Casper K. Larsen, Jens Leipziger, Mads Sorensen
Summary: K+-induced diuresis involves desensitization of the collecting duct to AVP.
Article
Multidisciplinary Sciences
Peder Berg, Jesper Frank Andersen, Mads Vaarby Sorensen, Tobias Wang, Hans Malte, Jens Leipziger
Summary: The lungs and kidneys play a crucial role in regulating the body's acid-base balance. In cystic fibrosis, impaired renal excretion of HCO3- leads to metabolic alkalosis, which can contribute to reduced lung function by suppressing ventilatory drive.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Nutrition & Dietetics
Nikita Misella Hansen, Peder Berg, Marianne Rix, Manan Pareek, Jens Leipziger, Anne -Lise Kamper, Arne Astrup, Mads Vaarby Sorensen, Louise Salomo
Summary: The objective of this study was to evaluate the effects of the New Nordic Renal Diet (NNRD) on metabolic acidosis and uremic toxins in patients with moderate CKD. The results showed that one week of NNRD effectively improved metabolic acidosis and reduced urinary excretion of uric acid and uremic toxins. These results provide encouragement for further investigations on the long-term renal protection effects of NNRD in patients with CKD.
JOURNAL OF RENAL NUTRITION
(2023)
Article
Biochemistry & Molecular Biology
Rainer Schreiber, Khaoula Talbi, Jiraporn Ousingsawat, Karl Kunzelmann
Summary: SIGIRR, PKP3, and TMEM16J are important factors that control immune response and inflammation. This study identifies TMEM16J as a calcium-activated calcium-permeable channel, which regulates intracellular calcium signals and the transcription and release of pro-inflammatory cytokines. TMEM16J may affect immune response in renal tissue and immune cells.
Article
Biochemistry & Molecular Biology
Karl Kunzelmann, Raquel Centeio, Jiraporn Ousingsawat, Khaoula Talbi, Ursula Seidler, Rainer Schreiber
Summary: SLC26A9 belongs to the SLC26A family of anion transporters and is expressed in the gastrointestinal tract, respiratory system, male tissues, and skin. It plays a modifier role in the gastrointestinal manifestation of cystic fibrosis (CF).
Article
Urology & Nephrology
Bidisha Saha, Waheed Shabbir, Enzo Takagi, Xin-Peng Duan, Deise Carla Almeida Leite Dellova, John Demko, Anna Manis, Dominique Loffing-Cueni, Johannes Loffing, Mads Vaarby Sorensen, Wen-Hui Wang, David Pearce
Summary: The mTORC2-SGK1-Nedd4-2-ENaC signaling axis plays a crucial role in the rapid renal responses to increased plasma potassium concentration. Other downstream targets of this signaling pathway, such as PKC and Akt, are not acutely affected, and ROMK and BK channels are not activated. These findings provide new insights into the signaling network and ion transport systems underlying renal responses to potassium in vivo.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Urology & Nephrology
Peder Berg, Tobias Jensen, Jesper Frank Andersen, Samuel L. Svendsen, Ida Maria Modvig, Tobias Wang, Sebastian Frische, Billy K. C. Chow, Hans Malte, Jens Juul Holst, Mads Vaarby Sorensen, Jens Leipziger
Summary: This study found that loss of SCTR impairs renal base excretion during acute metabolic alkalosis, and KO mice develop prolonged metabolic alkalosis after acute base loading. Additionally, the study found that increased blood alkalinity promotes secretin release from the small intestine and secretin is critical for bicarbonate homeostasis.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Multidisciplinary Sciences
H. Vitzthum, M. Koch, L. Eckermann, S. L. Svendsen, P. Berg, C. A. Huebner, C. A. Wagner, J. Leipziger, C. Meyer-Schwesinger, H. Ehmke
Summary: Maintaining acid-base balance is important for the kidneys, and the solute transporter AE4 in beta-intercalated cells is found to play a role in renal acid-base sensing mechanism.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Karl Kunzelmann, Jiraporn Ousingsawat, Andre Kraus, Julien H. Park, Thorsten Marquardt, Rainer Schreiber, Bjorn Buchholz
Summary: This article summarizes the common features of Cl--transporting proteins CFTR, SLC26A9, and anoctamin (ANO1; ANO6) in airway and renal diseases. Recent findings on electrolyte transport in the airways and kidneys, as well as the roles of CFTR, SLC26A9, ANO1, and ANO6 are reviewed. The article highlights the importance of CFTR as the main secretory Cl- channel in airways under basal and stimulated conditions, and provides information on the expressions and functions of ANO1 and ANO6, as well as the reabsorptive function of SLC26A9 in the airways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
