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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

Correlation and Bland-Altman plot for two different creatinine assay methods in two independent laboratories on same samples.Excellent correlation was obtained between these two methods (a) Konelab (KL) Jaffe and Roche Hitachi (RH) Jaffe, (b) Konelab (KL) Jaffe and Konelab (KL) enzymatic and (c) Roche Hitachi (RH) Jaffe and Konelab (KL) enzymatic.
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pone.0122357.g007: Correlation and Bland-Altman plot for two different creatinine assay methods in two independent laboratories on same samples.Excellent correlation was obtained between these two methods (a) Konelab (KL) Jaffe and Roche Hitachi (RH) Jaffe, (b) Konelab (KL) Jaffe and Konelab (KL) enzymatic and (c) Roche Hitachi (RH) Jaffe and Konelab (KL) enzymatic.

Mentions: Almost all patients had plasma paraquat concentrations below 10 mg/L and only one had a concentration greater than 100 mg/L. The current nomogram outcome prediction lines predicted death well in this cohort (Fig 6). The creatinine values assayed by both Jaffe methods were strongly correlated (bias 0.16, r = 0.98) (Fig 7A), and there was an excellent correlation also between the Konelab Jaffe and enzymatic method (bias 0.26, r = 0.98) (Fig 7B) and Roche Hitachi Jaffe and the enzymatic method (bias 0.1 and r = 0.93) (Fig 7C).


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)

Correlation and Bland-Altman plot for two different creatinine assay methods in two independent laboratories on same samples.Excellent correlation was obtained between these two methods (a) Konelab (KL) Jaffe and Roche Hitachi (RH) Jaffe, (b) Konelab (KL) Jaffe and Konelab (KL) enzymatic and (c) Roche Hitachi (RH) Jaffe and Konelab (KL) enzymatic.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0122357.g007: Correlation and Bland-Altman plot for two different creatinine assay methods in two independent laboratories on same samples.Excellent correlation was obtained between these two methods (a) Konelab (KL) Jaffe and Roche Hitachi (RH) Jaffe, (b) Konelab (KL) Jaffe and Konelab (KL) enzymatic and (c) Roche Hitachi (RH) Jaffe and Konelab (KL) enzymatic.
Mentions: Almost all patients had plasma paraquat concentrations below 10 mg/L and only one had a concentration greater than 100 mg/L. The current nomogram outcome prediction lines predicted death well in this cohort (Fig 6). The creatinine values assayed by both Jaffe methods were strongly correlated (bias 0.16, r = 0.98) (Fig 7A), and there was an excellent correlation also between the Konelab Jaffe and enzymatic method (bias 0.26, r = 0.98) (Fig 7B) and Roche Hitachi Jaffe and the enzymatic method (bias 0.1 and r = 0.93) (Fig 7C).

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