title: Mechanisms underlying early rapid increases in creatinine in paraquat poisoning.
abstract: BACKGROUND
  Acute kidney injury (AKI) is common after severe paraquat poisoning and usually heralds a fatal outcome. The rapid large increases in serum creatinine (Cr) exceed that which can be explained by creatinine kinetics based on loss of glomerular filtration rate (GFR).
  
  
  RESULTS
  This prospective multi-centre study compared the kinetics of two surrogate markers of GFR, serum creatinine and serum cystatin C (CysC), following paraquat poisoning to understand and assess renal functional loss after paraquat poisoning. Sixty-six acute paraquat poisoning patients admitted to medical units of five hospitals were included. Relative changes in creatinine and CysC were monitored in serial blood and urine samples, and influences of non-renal factors were also studied.
  
  
  RESULTS
  Forty-eight of 66 patients developed AKI (AKIN criteria), with 37 (56%) developing moderate to severe AKI (AKIN stage 2 or 3). The 37 patients showed rapid increases in creatinine of >100% within 24 hours, >200% within 48 hours and >300% by 72 hours and 17 of the 37 died. CysC concentration increased by 50% at 24 hours in the same 37 patients and then remained constant. The creatinine/CysC ratio increased 8 fold over 72 hours. There was a modest fall in urinary creatinine and serum/urine creatinine ratios and a moderate increase in urinary paraquat during first three days.
  
  
  CONCLUSIONS
  Loss of renal function contributes modestly to the large increases in creatinine following paraquat poisoning. The rapid rise in serum creatinine most probably represents increased production of creatine and creatinine to meet the energy demand following severe oxidative stress. Minor contributions include increased cyclisation of creatine to creatinine because of acidosis and competitive or non-competitive inhibition of creatinine secretion. Creatinine is not a good marker of renal functional loss after paraquat poisoning and renal injury should be evaluated using more specific biomarkers of renal injury.
authors: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka; Clinical Pharmacology and Toxicology Group, Professorial Medicine Unit, The Prince of Wales Clinical School, University of New South Wales, Sydney, Australia; Department of Pharmacy, Faculty of Allied Health Sciences, University of Peradeniya, Peradeniya, Sri Lanka; Department of Nephrology, Prince Of Wales Hospital and Clinical School, University of New South Wales, Sydney, Australia.
authors: Fahim
authors: F
authors: Mohamed
authors: Department of Nephrology, Prince Of Wales Hospital and Clinical School, University of New South Wales, Sydney, Australia.
authors: Zoltan
authors: Z
authors: Endre
authors: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka.
authors: Shaluka
authors: S
authors: Jayamanne
authors: Department of Nephrology, Prince Of Wales Hospital and Clinical School, University of New South Wales, Sydney, Australia.
authors: Timothy
authors: T
authors: Pianta
authors: Department of Nephrology, Prince Of Wales Hospital and Clinical School, University of New South Wales, Sydney, Australia.
authors: Philip
authors: P
authors: Peake
authors: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka.
authors: Chathura
authors: C
authors: Palangasinghe
authors: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka.
authors: Umesh
authors: U
authors: Chathuranga
authors: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka.
authors: Kithsiri
authors: K
authors: Jayasekera
authors: Therapeutics Research Centre, School of Medicine, University of Queensland, Brisbane, Australia.
authors: Klintean
authors: K
authors: Wunnapuk
authors: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka.
authors: Fathima
authors: F
authors: Shihana
authors: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka.
authors: Seyed
authors: S
authors: Shahmy
authors: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka; Clinical Pharmacology and Toxicology Group, Professorial Medicine Unit, The Prince of Wales Clinical School, University of New South Wales, Sydney, Australia; Department of Pharmacology, School of Medical Sciences, Sydney Medical School, University of Sydney, Sydney, Australia.
authors: Nicholas
authors: N
authors: Buckley
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000139:chemically induced / Q000652:urine; D000328:Adult; D015415:Biomarkers / Q000097:blood* / Q000652:urine; D003404:Creatinine / Q000097:blood* / Q000652:urine; D055316:Cystatin C / Q000097:blood* / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010269:Paraquat / Q000633:toxicity
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D003404:Creatinine; D010269:Paraquat