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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

Relative changes (%) in both creatinine and cystatin C.Total of 37 severe patients included in this graph (non-survivors = 17 patients). In all the survivors, baseline was assumed as lowest concentrations during the hospital stay or at follow up (for both serum creatinine and serum cystatin C). Baseline serum creatinine level in non-survivors was estimated by solving MDRD formula for GFR of 75 ml/min.
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pone.0122357.g003: Relative changes (%) in both creatinine and cystatin C.Total of 37 severe patients included in this graph (non-survivors = 17 patients). In all the survivors, baseline was assumed as lowest concentrations during the hospital stay or at follow up (for both serum creatinine and serum cystatin C). Baseline serum creatinine level in non-survivors was estimated by solving MDRD formula for GFR of 75 ml/min.

Mentions: In patients with higher severity AKI (AKIN 2 & 3) following paraquat, there was a 100% increase in median creatinine relative to baseline by 24 hours and 200% by 48 hours (Fig 3). The increase in creatinine was 300% relative to baseline by 72 hours. Because these changes were based largely on estimated baseline creatinine values, a sensitivity analysis was conducted to assess the effect of using different baseline assumptions for both serum creatinine and CysC. Seventy five percent (75%) of survivors had baseline creatinine levels below 0.9 mg/dl. Based on demographic similarity to survivors, the baseline level of non-survivors could be assumed to be 0.9 mg/dl. Using this estimate an even greater than 300% increase in creatinine was seen at 48 hours, and the apparent disparity between creatinine and CysC increased (Fig 4).


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)

Relative changes (%) in both creatinine and cystatin C.Total of 37 severe patients included in this graph (non-survivors = 17 patients). In all the survivors, baseline was assumed as lowest concentrations during the hospital stay or at follow up (for both serum creatinine and serum cystatin C). Baseline serum creatinine level in non-survivors was estimated by solving MDRD formula for GFR of 75 ml/min.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0122357.g003: Relative changes (%) in both creatinine and cystatin C.Total of 37 severe patients included in this graph (non-survivors = 17 patients). In all the survivors, baseline was assumed as lowest concentrations during the hospital stay or at follow up (for both serum creatinine and serum cystatin C). Baseline serum creatinine level in non-survivors was estimated by solving MDRD formula for GFR of 75 ml/min.
Mentions: In patients with higher severity AKI (AKIN 2 & 3) following paraquat, there was a 100% increase in median creatinine relative to baseline by 24 hours and 200% by 48 hours (Fig 3). The increase in creatinine was 300% relative to baseline by 72 hours. Because these changes were based largely on estimated baseline creatinine values, a sensitivity analysis was conducted to assess the effect of using different baseline assumptions for both serum creatinine and CysC. Seventy five percent (75%) of survivors had baseline creatinine levels below 0.9 mg/dl. Based on demographic similarity to survivors, the baseline level of non-survivors could be assumed to be 0.9 mg/dl. Using this estimate an even greater than 300% increase in creatinine was seen at 48 hours, and the apparent disparity between creatinine and CysC increased (Fig 4).

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