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Mechanisms underlying early rapid increases in creatinine in paraquat poisoning.

Mohamed F, Endre Z, Jayamanne S, Pianta T, Peake P, Palangasinghe C, Chathuranga U, Jayasekera K, Wunnapuk K, Shihana F, Shahmy S, Buckley N - PLoS ONE (2015)

Bottom Line: 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.Minor contributions include increased cyclisation of creatine to creatinine because of acidosis and competitive or non-competitive inhibition of creatinine secretion.

View Article: PubMed Central - PubMed

Affiliation: 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.

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).

Methods and findings: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Serial serum concentrations of creatinine and cystatin C relative to AKI and hospital discharge status.This figure represents the changes in absolute creatinine (a & b) and cystatin C (c & d) concentrations in each patients over 4 days following paraquat ingestion. Filled symbols represent patients who died in the hospital and the open symbols represent survivors. Patients were also grouped according to AKI severity; No-AKI (black triangle), AKIN1 (blue rhombus), AKIN2 (green square) and AKIN3 (red circles).
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pone.0122357.g002: Serial serum concentrations of creatinine and cystatin C relative to AKI and hospital discharge status.This figure represents the changes in absolute creatinine (a & b) and cystatin C (c & d) concentrations in each patients over 4 days following paraquat ingestion. Filled symbols represent patients who died in the hospital and the open symbols represent survivors. Patients were also grouped according to AKI severity; No-AKI (black triangle), AKIN1 (blue rhombus), AKIN2 (green square) and AKIN3 (red circles).

Mentions: Sixty six (n = 66) patients were available for evaluation and 48 developed AKI. Of patients with AKI, 37 developed moderate to severe AKI (AKIN stage 2 and 3) and seventeen (n = 17) of these died in the hospital. Development of AKI was associated with death in the entire cohort (n = 66 patients, RR = 1.5, OR = 20, p<0.005) (Fig 1). Limited renal replacement therapy was available for the entire hospital and was not offered to patients following paraquat or other herbicide poisonings. Patients were predominantly young, previously healthy males with similar baseline demographic and clinical variables regardless of outcome except for baseline serum creatinine and estimated GFR (Table 1). Estimated baseline serum creatinine was higher in non-survivors, which probably reflects an over estimate in these young patients since creatinine was back-calculated using MDRD75 in all non-survivors [11]. In both survivors and non-survivors, AKI was generally moderate to severe (stage 2 or 3) with rapid increases in serum creatinine concentrations observed in half of the cohort (n = 37). In contrast, creatinine concentration remained relatively unchanged or gradually increased in less severe AKI groups (AKIN1) and in non-AKI (Fig 2). Further analysis was restricted to the 37 moderate to severe AKI cases to explore the causal factors accounting for the observed rapid rise in creatinine in these patients and also observed in similar studies [3,6,14].


Mechanisms underlying early rapid increases in creatinine in paraquat poisoning.

Mohamed F, Endre Z, Jayamanne S, Pianta T, Peake P, Palangasinghe C, Chathuranga U, Jayasekera K, Wunnapuk K, Shihana F, Shahmy S, Buckley N - PLoS ONE (2015)

Serial serum concentrations of creatinine and cystatin C relative to AKI and hospital discharge status.This figure represents the changes in absolute creatinine (a & b) and cystatin C (c & d) concentrations in each patients over 4 days following paraquat ingestion. Filled symbols represent patients who died in the hospital and the open symbols represent survivors. Patients were also grouped according to AKI severity; No-AKI (black triangle), AKIN1 (blue rhombus), AKIN2 (green square) and AKIN3 (red circles).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376530&req=5

pone.0122357.g002: Serial serum concentrations of creatinine and cystatin C relative to AKI and hospital discharge status.This figure represents the changes in absolute creatinine (a & b) and cystatin C (c & d) concentrations in each patients over 4 days following paraquat ingestion. Filled symbols represent patients who died in the hospital and the open symbols represent survivors. Patients were also grouped according to AKI severity; No-AKI (black triangle), AKIN1 (blue rhombus), AKIN2 (green square) and AKIN3 (red circles).
Mentions: Sixty six (n = 66) patients were available for evaluation and 48 developed AKI. Of patients with AKI, 37 developed moderate to severe AKI (AKIN stage 2 and 3) and seventeen (n = 17) of these died in the hospital. Development of AKI was associated with death in the entire cohort (n = 66 patients, RR = 1.5, OR = 20, p<0.005) (Fig 1). Limited renal replacement therapy was available for the entire hospital and was not offered to patients following paraquat or other herbicide poisonings. Patients were predominantly young, previously healthy males with similar baseline demographic and clinical variables regardless of outcome except for baseline serum creatinine and estimated GFR (Table 1). Estimated baseline serum creatinine was higher in non-survivors, which probably reflects an over estimate in these young patients since creatinine was back-calculated using MDRD75 in all non-survivors [11]. In both survivors and non-survivors, AKI was generally moderate to severe (stage 2 or 3) with rapid increases in serum creatinine concentrations observed in half of the cohort (n = 37). In contrast, creatinine concentration remained relatively unchanged or gradually increased in less severe AKI groups (AKIN1) and in non-AKI (Fig 2). Further analysis was restricted to the 37 moderate to severe AKI cases to explore the causal factors accounting for the observed rapid rise in creatinine in these patients and also observed in similar studies [3,6,14].

Bottom Line: 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.Minor contributions include increased cyclisation of creatine to creatinine because of acidosis and competitive or non-competitive inhibition of creatinine secretion.

View Article: PubMed Central - PubMed

Affiliation: 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.

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).

Methods and findings: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus