Abstract
The kidney is the second most frequent target of serious adverse effects of non-steroidal antiinflammatory drugs (NSAIDs). The renal side effects of NSAIDs related to inhibition of cyclooxygenase (COX) comprise reduction in renal blood flow (RBF) and glomerular filtration rate (GFR), sodium/water retention, water intoxication and hyperkalemia. The discovery of two COX-isoenzymes, a constitutive COX-1, serving homeostatic prostanoid synthesis, and an inducible COX-2, responsible for proinflammatory prostanoid production, led to the development of new NSAIDs: Preferential and specific COX-2 inhibitors, promising minimal NSAIDtypical toxicity with equivalent efficacy. However, we learned that there is no clear distinction in “physiologic” constitutive COX-1 and “inflammatory” inducible COX-2. This is particular true for the kidney of humans and other mammalians, where COX-2 was found constitutively in meaningful amounts. Animal experiments and clinical trials with preferential and specific COX-2 inhibitors revealed that COX-2 is the critical enzyme for sodium excretion, renin release and likely antagonism of antidiuretic hormone. Additionally, a significant role of COX-2 for nephrogenesis is suggested. For renal hemodynamics the given evidence point to COX-1 as the predominant enzyme, but further investigations are required. In summary, the gain of renal safety by use of preferential or specific COX-2 inhibitors is small or negligible with respect to sodium retention, hyperkalemia and probably water intoxication. These drugs may be advantageous regarding renal perfusion, but presently the same precautions as for conventional NSAIDs must be used.
Current Pharmaceutical Design
Title: COX-2 and the Kidneys
Volume: 6 Issue: 17
Author(s): D. O. Stichtenoth and J. C. Frolich
Affiliation:
Abstract: The kidney is the second most frequent target of serious adverse effects of non-steroidal antiinflammatory drugs (NSAIDs). The renal side effects of NSAIDs related to inhibition of cyclooxygenase (COX) comprise reduction in renal blood flow (RBF) and glomerular filtration rate (GFR), sodium/water retention, water intoxication and hyperkalemia. The discovery of two COX-isoenzymes, a constitutive COX-1, serving homeostatic prostanoid synthesis, and an inducible COX-2, responsible for proinflammatory prostanoid production, led to the development of new NSAIDs: Preferential and specific COX-2 inhibitors, promising minimal NSAIDtypical toxicity with equivalent efficacy. However, we learned that there is no clear distinction in “physiologic” constitutive COX-1 and “inflammatory” inducible COX-2. This is particular true for the kidney of humans and other mammalians, where COX-2 was found constitutively in meaningful amounts. Animal experiments and clinical trials with preferential and specific COX-2 inhibitors revealed that COX-2 is the critical enzyme for sodium excretion, renin release and likely antagonism of antidiuretic hormone. Additionally, a significant role of COX-2 for nephrogenesis is suggested. For renal hemodynamics the given evidence point to COX-1 as the predominant enzyme, but further investigations are required. In summary, the gain of renal safety by use of preferential or specific COX-2 inhibitors is small or negligible with respect to sodium retention, hyperkalemia and probably water intoxication. These drugs may be advantageous regarding renal perfusion, but presently the same precautions as for conventional NSAIDs must be used.
Export Options
About this article
Cite this article as:
Stichtenoth O. D. and Frolich C. J., COX-2 and the Kidneys, Current Pharmaceutical Design 2000; 6 (17) . https://dx.doi.org/10.2174/1381612003398717
DOI https://dx.doi.org/10.2174/1381612003398717 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
?Revolutionizing Cancer Treatment: Nano-Therapeutics Targeting Tumor Microenvironment?
This thematic issue explores the forefront of cancer treatment, centering on the groundbreaking potential of nano-therapeutics meticulously designed to target the tumor microenvironment. At its core, the issue aims to unravel the latest advancements in nanotechnology, showcasing innovative materials, formulations, and delivery systems that hold promise for redefining cancer therapeutics. ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Crosstalk between Oxidative and Nitrosative Stress and Arterial Stiffness
Current Vascular Pharmacology The p53-p66Shc Apoptotic Pathway is Dispensable for Tumor Suppression whereas the p66Shc-generated Oxidative Stress Initiates Tumorigenesis
Current Pharmaceutical Design Fragmented ECG as a Risk Marker in Cardiovascular Diseases
Current Cardiology Reviews Is Atherothromboaspiration a Possible Solution for the Prevention of No-Reflow Phenomenon in Acute Coronary Syndromes? Single Centre Experience and Review of the Literature
Current Vascular Pharmacology Nitric Oxide Mimetic Molecules as Therapeutic Agents in Alzheimers Disease
Current Alzheimer Research Therapeutic Potential of Erythropoietin in Retinal and Optic Nerve Diseases
CNS & Neurological Disorders - Drug Targets Comparative Effectiveness of Pioglitazone and Rosiglitazone in Type 2 Diabetes, Prediabetes,and the Metabolic Syndrome: A Meta-Analysis
Current Diabetes Reviews Current Management of Vascular Tumors in the Neonate
Current Pediatric Reviews Efficacy of Cangrelor as Bridging Therapy Post PCI
Cardiovascular & Hematological Disorders-Drug Targets Recent Progress in the Therapeutic Role of Serelaxin in Vascular Dysfunction
Current Protein & Peptide Science Profiling the Shear Stress of Atherosclerosis; A Genomic View
Current Genomics In vivo Piroxicam Metabolites: Possible Source for Synthesis of Central Nervous System (CNS) Acting Depressants
Central Nervous System Agents in Medicinal Chemistry Anesthetic-induced Myocardial Conditioning: Molecular Fundamentals and Scope
Current Medicinal Chemistry Approaches to the Management of Acute Kidney Injury in Children
Recent Patents on Biomarkers Ras Family Small GTPase-Mediated Neuroprotective Signaling in Stroke
Central Nervous System Agents in Medicinal Chemistry Physiology of Folic Acid in Health and Disease
Current Drug Metabolism Cyclin-Dependent Kinase 4/6 (Cdk4/6) Inhibitors: Perspectives in Cancer Therapy and Imaging
Mini-Reviews in Medicinal Chemistry Multiple Roles of Histamine in Autoimmune Demyelinating Disease of the Central Nervous System
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Role of Wnt Signaling in Tissue Fibrosis, Lessons from Skeletal Muscle and Kidney
Current Molecular Medicine Effects of Blood Pressure Control in Cardiovascular Prevention
Current Pharmaceutical Design