Structures already discussed alongside renal tubular transport disease in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
RCSB Protein Data Bank · entry 5KM8 · 2.0 Å · ligand Cidofovir (L8P). Experimental structure, not a prediction.
The 2019 review of inherited kidney disorders explains that monogenic kidney diseases are caused by mutations in genes coding for receptors, channels, transporters, enzymes, transcription factors, and structural components. These mutations disrupt transport processes in specialised cell types along the nephron, including the proximal tubule, where dysfunction leads to renal Fanconi syndrome, and segments handling glucose, uric acid, sodium, calcium, and magnesium reabsorption. The 2016 review on renal drug transporters notes that these proteins, located primarily in the proximal tubules, mediate tubular secretion and reabsorption of organic cations and anions, and are increasingly recognised as targets for clinically significant drug–drug interactions. No abstract reports a trial of any drug specifically for renal tubular transport disease.
The 2009 review of emerging therapy-related kidney disease describes renal toxicities from newer medications introduced in the preceding decade. These therapies can cause acute or chronic glomerular, tubular, interstitial, or vascular injury, and some changes are irreversible, leading to end-stage renal disease. The 2023 simplified approach to paediatric renal tubular disorders states that the tubular system reabsorbs 99% of glomerular ultrafiltrate—roughly 180 litres per day—including electrolytes, glucose, amino acids, bicarbonate, phosphate, and low-molecular-weight proteins. That review discusses when to suspect a disorder and lists specific mutations for a few common conditions, but provides no treatment data.
No abstract reports a drug repurposed for renal tubular transport disease. No survival or response rates are given for any intervention. What is missing is any clinical trial testing a drug in patients with these disorders, any patient stratification by mutation or transporter subtype, and dedicated funding for such studies.
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Acta Pharmaceutica Sinica B · 2016 · 190 citations · open access
Renal drug transporters and their significance in drug–drug interactions
AbstractThe kidney is a vital organ for the elimination of therapeutic drugs and their metabolites. Renal drug transporters, which are primarily located in the renal proximal tubules, play an important role in tubular secretion and reabsorption of drug molecules in the kidney. Tubular secretion is characterized by high clearance capacities, broad substrate specificities, and distinct charge selectivity for organic cations and anions. In the past two decades, substantial progress has been made in understanding the roles of transporters in drug disposition, efficacy, toxicity and drug-drug interactions (DDIs). In the kidney, several transporters are involved in renal handling of organic cation (OC) and organic anion (OA) drugs. These transporters are increasingly recognized as the target for clinically significant DDIs. This review focuses on the functional characteristics of major human renal drug transporters and their involvement in clinically significant DDIs.
https://doi.org/10.1016/j.apsb.2016.07.013The Journal of Infectious Diseases · 1978 · 109 citations
The Nephrotoxicity of Cephalosporins: An Overview
AbstractThe cephalosporin antibiotics cephaloridine and cephalothin are known to cause renal damage. Experience with newer congeners is not yet sufficient to predict their potential nephrotoxocity. The renal lesion produced by cephaloridine is primarily due to the intrinsic toxicity of this drug for the cells of the proximal renal tubule and depends upon its peculiar transport characteristics. In contrast, renal injury due to cephalothin resembles that seen with the penicillins. Thus, some instances of cephalothin nephropathy appear to be toxic in nature with a histologic picture of acute tubular necrosis, whereas others exhibit signs of hypersensitivity including rash, eosinophilia, and interstitial nephritis. Among the factors alleged to contribute to the nephrotoxicity of cephalosporins is their administration with aminoglycosides. Although the physician should be aware of the possibility of a potential adverse interaction between these groups of antibiotics, the evidence is not sufficiently conclusive to warrant avoidance of the combination when it appears to be therapeutically useful.
https://doi.org/10.1093/infdis/137.supplement.s60Physiological Reviews · 2019 · 78 citations · open access
Learning Physiology from Inherited Kidney Disorders
AbstractThe identification of genes causing inherited kidney diseases yielded crucial insights in the molecular basis of disease and improved our understanding of physiological processes that operate in the kidney. Monogenic kidney disorders are caused by mutations in genes coding for a large variety of proteins including receptors, channels and transporters, enzymes, transcription factors, and structural components, operating in specialized cell types that perform highly regulated homeostatic functions. Common variants in some of these genes are also associated with complex traits, as evidenced by genome-wide association studies in the general population. In this review, we discuss how the molecular genetics of inherited disorders affecting different tubular segments of the nephron improved our understanding of various transport processes and of their involvement in homeostasis, while providing novel therapeutic targets. These include inherited disorders causing a dysfunction of the proximal tubule (renal Fanconi syndrome), with emphasis on epithelial differentiation and receptor-mediated endocytosis, or affecting the reabsorption of glucose, the handling of uric acid, and the reabsorption of sodium, calcium, and magnesium along the kidney tubule.
https://doi.org/10.1152/physrev.00008.2018Transplantation · 2002 · 75 citations
Topical use of cidofovir induced acute renal failure
AbstractBACKGROUND: Cidofovir has antiviral activity against a wide spectrum of DNA viruses. Several small studies have focused on the efficacy of topical cidofovir in various viral-induced diseases. We report a systemic complication of such therapy. CASE REPORT: A bone marrow transplant recipient with chronic renal failure developed genital condylomas resistant to standard therapy. After topical cidofovir application (1% once daily for 5 days, then 4% for 12 days), the lesions improved while local erosions appeared. Acute renal failure with features of tubular acidosis occurred at day 19. Spontaneous recovery was observed after cidofovir withdrawal. CONCLUSION: We describe for the first time acute renal failure after topical cidofovir in an immunosuppressed patient with prior renal insufficiency. This method of administration should be avoided on abraded skin and should be carefully monitored.
https://doi.org/10.1097/00007890-200202270-00033Annals of Internal Medicine · 1960 · 16 citations
THE EFFECT OF THIAZIDE DIURETICS ON THE ABNORMAL KIDNEY
AbstractArticle30 December 1960THE EFFECT OF THIAZIDE DIURETICS ON THE ABNORMAL KIDNEYLEONARD S. DREIFUS, M.D., CRISTOBAL DUARTE, M.D., RYUICHI KODAMA, M.D., JOHN H. MOYER, M.D.LEONARD S. DREIFUS, M.D.Search for more papers by this author, CRISTOBAL DUARTE, M.D.Search for more papers by this author, RYUICHI KODAMA, M.D.Search for more papers by this author, JOHN H. MOYER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-53-6-1170 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThiazide diuretics have been used with rather favorable results in the presence of renal disease.1-4Furthermore, several investigators1, 4-7have reported a low incidence of toxicity with the use of these drugs in patients with normal as well as with diseased kidneys. On the other hand, patients with liver disease and ascites appeared to be less responsive to these agents. Chlorothiazide, given to patients with cirrhosis, was associated with a reduction in serum potassium and a concomitant increase in the blood pH. Beyer6has demonstrated the effectiveness of chlorothiazide in the presence of both acidosis and alkalosis. Chlorothiazide will enhance...Bibliography1. LaraghHeinemannDemartini JHHOFE: The effect of chlorothiazide on electrolyte transport in man: its use in treatment of edema in congestive heart failure, nephrosis, and cirrhosis, J. A. M. A. 166: 145, 1958. CrossrefMedlineGoogle Scholar2. Pitts RF: Some reflections on mechanisms of action of diuretics, Am. J. Med. 24: 745, 1958. CrossrefMedlineGoogle Scholar3. SchreinerBloomer GEHA: The effect of chlorothiazide (Diuril) on the edema of cirrhosis, nephrosis, congestive heart failure, and chronic renal insufficiency, New England J. Med. 257: 1016, 1957. CrossrefMedlineGoogle Scholar4. Schreiner GE: Chlorothiazide in renal disease, Ann. New York Acad. Sc. 71: 420, 1958. CrossrefMedlineGoogle Scholar5. BaylissMarrackPirkisReesZilva RIDJJRJF: The use of chlorothiazide in the treatment of edema, Ann. New York Acad. Sc. 71: 442, 1958. CrossrefMedlineGoogle Scholar6. Beyer KH: The mechanism of action of chlorothiazide, Ann. New York Acad. Sc. 71: 363, 1958. CrossrefMedlineGoogle Scholar7. HeiderDennisMoyer CEJH: Chlorothiazide potentiation of ganglionic blockage in patients with hypertension, Ann. New York Acad. Sc. 71: 456, 1958. CrossrefMedlineGoogle Scholar8. StamlerDreifusKatz JLSLN: Response to rapid water, sodium, and dextran loads in intact Ringer's-infused unanesthetized dogs, Am. J. Physiol. 195: 362, 1958. CrossrefMedlineGoogle Scholar9. HeinemannDemartiniLaragh HOFEJH: The effect of chlorothiazide on renal excretion of electrolytes and free water, Am. J. Med. 26: 853, 1959. CrossrefMedlineGoogle Scholar10. JanuszewiczHeinemannDemartiniLaragh WHOFEJH: A clinical study of the effects of hydrochlorothiazide on the renal excretion of electrolytes and free water, New England J. Med. 261: 264, 1959. CrossrefMedlineGoogle Scholar11. DuarteKodamaBrestMoyerDreifus CRAJHLS: Uric acid excretion patterns in hypertensive renal disease, gouty arthritis, and normal subjects following intravenous hydrochlorothiazide, in preparation. Google Scholar12. UessonAnslow LGWP: Effect of osmotic and mercurial diuretics on simultaneous water diuresis, Am. J. Physiol. 170: 255, 1952. CrossrefMedlineGoogle Scholar13. ZakBrunSmith CACHW: The mechanism of formation of osmotically concentrated urine during the anti-diuretic state, J. Clin. Investigation 33: 1064, 1954. CrossrefMedlineGoogle Scholar14. SherlockReadLaidlawHaslam SAEJLR: Chlorothiazide in liver disease, Ann. New York Acad. Sci. 71: 430, 1958. CrossrefMedlineGoogle Scholar15. FriedmanGoldbergCastlemanGoldstein ISMLJD: Chlorothiazide and electrolyte depletion in chronic glomerulonephritis, Arch. Int. Med. 105: 7, 1960. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pennsylvania*Received for publication April 6, 1960.From the Section of Hypertensive and Renal Diseases, Department of Medicine, Hahnemann Medical College and Hospital, Philadelphia, Pennsylvania.†These studies were supported by the Heart Association of Southeastern Pennsylvania, and a grant from the National Institutes of Health, Bethesda, Md. (H 3511).This paper was presented in part at the Regional Meeting of the Eastern Section of The American College of Physicians, January 30, 1960, Philadelphia, Pennsylvania.‡Fellow in Hypertension and Renology.Requests for reprints should be addressed to Leonard S. Dreifus, M.D., Hahnemann Medical College and Hospital, Philadelphia 2, Pennsylvania. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMPQTCHPharmacodynamics and kinetics of etozolin/ozolinone in hypertensive patients with normal and impaired kidney functionPharmacodynamics and pharmacokinetics of xipamide in patients with normal and impaired kidney functionPharmacokinetics in pregnancyPathological and Physiological Factors Affecting Drug Absorption, Distribution, Elimination, and Response in ManThiazide Diuretics and Related DrugsUSE OF A DIURETIC COMBINATION OF TRIAMTERENE AND HYDROCHLOROTHIAZIDE IN ELDERLY PATIENTSManagement of chronic renal failurePHARMACOLOGIC ASPECTS OF AGING: A SURVEY OF THE EFFECT OF INCREASING AGE ON DRUG ACTIVITY IN ADULTSRole of Diuretic Agents in the Management of Renal Disease 30 December 1960Volume 53, Issue 6Page: 1170-1179KeywordsAttentionBlood plasmaDiureticsExcretionHospital medicinePotassiumRenal diseasesToxicityUreaUric acid Issue Published: 30 December 1960 PDF downloadLoading ...
https://doi.org/10.7326/0003-4819-53-6-1170PubMed · 2009 · 4 citations
Emerging therapy-related kidney disease.
AbstractCONTEXT: Many new therapies have emerged within the last 5 to 10 years to treat a variety of conditions. Several of these have direct or indirect renal toxicities that may go undiagnosed without careful attention of the pathologist to a patient's clinical history, particularly the addition of new medications or treatments. OBJECTIVE: To discuss patterns of renal injury resulting from medications or therapeutic regimens that have been introduced within the last 10 years. Recognition of these patterns may allow the pathologist to alert the attending clinician to a possible drug-induced renal injury and prevent further deterioration of renal function and possible chronic kidney disease. DATA SOURCES: A review of recent literature and unpublished observations of case-derived material. CONCLUSIONS: A number of newer therapies have emerged as agents of renal toxicity, producing a variety of pathologic changes in the kidney. The outcome can be acute or chronic glomerular, tubular, interstitial, and/or vascular injury. Some drugs will result in irreversible changes and end-stage renal disease, whereas many of the alterations can be reversed with removal of the offending agent, avoiding potential long-term kidney injury.
https://doi.org/10.5858/133.2.268Indian Journal of Child Health · 2023 · 0 citations · open access
Demystifying Renal Tubular Disorders in children : A simplified approach
AbstractRenal tubular disorders essentially include all disorders of the highly specialized channels of the renal tubular system, from the proximal convoluted tubule to the cortical and medullary collecting ducts. This tubular system is responsible for reabsorption of 99% of glomerular ultrafiltrate, which contains a large amount of fluid (approximately 180 L/day) as well as most electrolytes and many metabolites such as glucose (G), amino acids, bicarbonate (HCO3-), phosphate (PO4 3-), and low-molecular-weight proteins and is essential for maintaining fluid, electrolyte, and acid–base balance. In this review, we will briefly discuss when to suspect a renal tubular disorder, a simplified algorithm for evaluation, and specific mutations of a few common disorders.
https://doi.org/10.32677/ijch.v9i12.3725Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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