[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-435647-105":59,"doc-detail-435647-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","cilastatin-a-promising-solution-for-acute-kidney-injury-editorial","Cilastatin a promising solution for acute kidney injury - Editorial","","Acute kidney injury (AKI) affects millions worldwide and remains difficult to prevent or reverse with reliable pharmacologic options. Current care is largely supportive and reactive, while fluid overload and ongoing exposure to nephrotoxins worsen incidence, severity, mortality, and recovery. Cilastatin is reviewed as a renal tubular dehydropeptidase-1 (DHP-1) inhibitor that protects the kidney by limiting megalin-mediated uptake of nephrotoxic drugs, reducing ROS, apoptosis, and inflammatory signaling. Evidence from preclinical models and emerging human studies highlights improved serum creatinine and reduced AKI risk, including in patients receiving imipenem-cilastatin.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/cilastatin-a-promising-solution-for-acute-kidney-injury-editorial/435647/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/cilastatin-a-promising-solution-for-acute-kidney-injury-editorial/435647.png","ImageObject",300,407,{"name":92,"@type":93},"LangkahRina","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What makes acute kidney injury (AKI) difficult to treat preventively?","Question",{"text":112,"@type":113},"AKI often arises as a complication from nephrotoxic drugs, sepsis, and ischemia, and there is no single reliable pharmacologic intervention to prevent or reverse it. Current strategies are mainly supportive and reactive.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does cilastatin provide nephroprotection?",{"text":117,"@type":113},"Cilastatin selectively inhibits megalin-driven uptake of nephrotoxic compounds, reducing intracellular accumulation that triggers ROS and cellular injury. It also lowers ROS and apoptosis and downregulates pro-inflammatory cytokines while stabilizing mitochondrial membranes.",{"name":119,"@type":110,"acceptedAnswer":120},"What does the evidence suggest about imipenem-cilastatin and AKI risk?",{"text":121,"@type":113},"Research in animals and in vitro models shows reduced tubular necrosis and less creatinine elevation. Human evidence from pooled studies reports a reduced risk of AKI and lower serum creatinine in patients receiving imipenem-cilastatin compared with other antibiotics, with benefits consistent across study types.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},435647,1790760013,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":81,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":39},962090893776,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Editorial  \nCilastatin a promising solution for acute kidneyinjury by targeting nephrotoxicity  \nMuhammad Shaheer Bin Faheem, MBBSa , Syed Tawassul Hassan, MBBSb , Muhammad Idrees Khan, MDc ,*  \n# Background\n\nAcute kidney injury (AKI) refers to a condition in which thekidney fails to filter the waste products from the blood. It hasaffected 13 million people worldwide and caused 1.7–2.3 millionmortalities[1] . It remained a continuous challenge for both clin -icians and patients, and despite the years of progress in under -standing its pathophysiology, we still lack a single reliablepharmacologic intervention capable of preventing or reversingthis condition. Our kidneys are remarkably resilient, yet para -doxically fragile, especially when encountered with nephrotoxicdrugs, sepsis, and ischemia. Across the hospitals around theglobe, AKI frequently occurs as a complication leading to long -term renal impairment and mortality, with global estimatesrepresenting 25% AKI prevalence in hospitalized adults, withrates increasing up to 66% in intensive care units and limitedresource settings[1,2] .  \nCurrent management strategies indeed play a supportive rolein rehydrating, optimizing hemodynamics, and avoiding furthernephrotoxins, but in truth, these are stopgap measures that arereactive rather than preventive. Fluids and diuretics can help inmaintaining perfusion, but their excessive administration, espe -cially after initial resuscitation, leads to fluid overload (FO),which increases venous and renal interstitial pressures andimpairs renal perfusion, resulting in worse AKI outcomes[3] .Thus, the FO is associated with increased AKI incidence, greaterAKI severity, higher mortality, prolonged mechanical ventila -tion, and reduced renal recovery[3] . Even mild-to-moderate FO(≥5–10% of body weight) early in the ICU or post-surgery islinked to worse outcomes[3] . This therapeutic stagnation under -scores that we are still in need of a drug that can protect thekidneys before injury begins. Among potential candidates, clias -tatin, a renal tubular dehydropeptidase-1 (DHP-1) inhibitor  \naDepartment of Medicine, Karachi Institute of Medical Sciences, KIMS, Karachi,Sindh, Pakistan, bDepartment of Medicine, Karachi Medical and Dental College,KMDC, Karachi, Sindh, Pakistan and cDepartment of Medicine, Adam UniversitySchool of Medicine, Bishkek, Chuy region, Kyrgyzstan  \nSponsorships or competing interests that maybe relevant to content are disclosedatthe end of this article.  \n*Corresponding author. Address: Department of Medicine, Adam University School ofMedicine, Bishkek, Chuy region, Kyrgyzstan 720000. Email: dridrees666@gmail.com(M.I. Khan).  \nCopyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is anopen access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where itis permissible todownload and share the work provided itis properly cited. The work cannot bechanged in any way or used commercially without permission from the journal.  \nAnnals of Medicine & Surgery (2026) 88:19–21Received 19 July 2025; Accepted 5 November 2025Published online 25 November 2025http://dx.doi.org/10.1097/MS9.0000000000004336  \noriginally developed to stabilize imipenem, is now being recon -sidered for protecting the kidney from drug-induced injury.  \n# Mechanisms of nephroprotection\n\nCilastatin’s protective reputation rests primarily on its ability tointerfere with megalin-mediated endocytosis. Megalin isa multiligand receptor that is highly expressed on proximaltubular cells. It’s essential for reabsorbing filtered proteins andpeptides, but unfortunately, it also acts as a gateway for severalnephrotoxic drugs such as aminoglycosides, colistin, and vanco -mycin, allowing them to accumulate intracellularly and triggerthe generation of reactive oxygen species (ROS) and cellularinjury[4] . However, cilastatin selectively inhibits the megalin -driven uptake of the","cbCaimPS87acicxW","https://ap.wps.com/l/cbCaimPS87acicxW","pdf",205377,"English","# Background\n## Mechanisms of nephroprotection\n## Current evidence: preclinical and clinical insights","[{\"question\":\"What makes acute kidney injury (AKI) difficult to treat preventively?\",\"answer\":\"AKI often arises as a complication from nephrotoxic drugs, sepsis, and ischemia, and there is no single reliable pharmacologic intervention to prevent or reverse it. Current strategies are mainly supportive and reactive.\"},{\"question\":\"How does cilastatin provide nephroprotection?\",\"answer\":\"Cilastatin selectively inhibits megalin-driven uptake of nephrotoxic compounds, reducing intracellular accumulation that triggers ROS and cellular injury. It also lowers ROS and apoptosis and downregulates pro-inflammatory cytokines while stabilizing mitochondrial membranes.\"},{\"question\":\"What does the evidence suggest about imipenem-cilastatin and AKI risk?\",\"answer\":\"Research in animals and in vitro models shows reduced tubular necrosis and less creatinine elevation. Human evidence from pooled studies reports a reduced risk of AKI and lower serum creatinine in patients receiving imipenem-cilastatin compared with other antibiotics, with benefits consistent across study types.\"}]","Cilastatin a promising solution for acute kidney injury - Editorial | PDF",1790674538]