Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitrilotriacetate (NTA), an effective metal-chelating agent, has been used as a substitute for polyphosphates in household laundry detergents. Nephrotoxicity and renal tumorigenicity have been reported in experimental animals that received high doses of NTA po for 4 weeks to 2 years. Since NTA exists in water as a variety of NTA-metal complexes, it was important to investigate the biological effects of NTA in a complexed form. In this study, acute and subchronic toxicity of a ferric iron chelate of NTA (Fe-NTA) was investigated in rats. When Fe-NTA was given ip, acute tubular necrosis and renal failure occurred following a single injection of 15 mg iron/kg. Repeated injections of sublethal doses produced degeneration and necrosis of the proximal tubular epithelium and was associated with polyuria, glucosuria, aminoaciduria, and azotemia. After 9 days of treatment, regeneration of the tubular epithelium with atypical cells was observed. Except for a parenchymal iron deposit, no marked changes were observed in other organs. None of these effects were observed in animals given noncomplexed NTA. In conclusion, the toxicity observed following high doses of NTA given po may be the result of an absorbed metal-NTA chelate.
 ...
PMID:Acute renal failure and glucosuria induced by ferric nitrilotriacetate in rats. 397 99

The ingestion of paraquat, a non-selective herbicide, can be fatal in humans. Paraquat is toxic to multiple organs, including the kidney, heart, gastrointestinal tract and central nervous system. Although paraquat has been established as one cause of acute tubular necrosis, Fanconi syndrome presenting as severe hypophosphataemia after paraquat intoxication has not been reported. Here, we report the case of a 44-year-old Korean woman who presented with generalized proximal tubular dysfunction including aminoaciduria, phosphaturia and glycosuria after paraquat intoxication. We found that severe hypophosphataemia induces deep drowsiness. Renal biopsy findings indicated the presence of acute tubular necrosis that may be reversible.
 ...
PMID:Paraquat-induced Fanconi syndrome. 1622 Oct 89

Coronavirus disease 2019 (COVID-19) is commonly associated with kidney damage, and the angiotensin converting enzyme 2 (ACE2) receptor for SARS-CoV-2 is highly expressed in the proximal tubule cells. Whether patients with COVID-19 present specific manifestations of proximal tubule dysfunction remains unknown. To test this, we examined a cohort of 49 patients requiring hospitalization in a large academic hospital in Brussels, Belgium. There was evidence of proximal tubule dysfunction in a subset of patients with COVID-19, as attested by low-molecular-weight proteinuria (70-80%), neutral aminoaciduria (46%), and defective handling of uric acid (46%) or phosphate (19%). None of the patients had normoglycemic glucosuria. Proximal tubule dysfunction was independent of pre-existing comorbidities, glomerular proteinuria, nephrotoxic medications or viral load. At the structural level, kidneys from patients with COVID-19 showed prominent tubular injury, including in the initial part of the proximal tubule, with brush border loss, acute tubular necrosis, intraluminal debris, and a marked decrease in the expression of megalin in the brush border. Transmission electron microscopy identified particles resembling coronaviruses in vacuoles or cisternae of the endoplasmic reticulum in proximal tubule cells. Among features of proximal tubule dysfunction, hypouricemia with inappropriate uricosuria was independently associated with disease severity and with a significant increase in the risk of respiratory failure requiring invasive mechanical ventilation using Cox (adjusted hazard ratio 6.2, 95% CI 1.9-20.1) or competing risks (adjusted sub-distribution hazard ratio 12.1, 95% CI 2.7-55.4) survival models. Thus, our data establish that SARS-CoV-2 causes specific manifestations of proximal tubule dysfunction and provide novel insights into COVID-19 severity and outcome.
 ...
PMID:SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule. 3291 78