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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

Daily GFR estimates in paraquat patients.GFR was estimated based on serum cystatin C and creatinine and demonstrated a twofold higher GFR for estimation based on cystatin C estimates than creatinine.
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pone.0122357.g005: Daily GFR estimates in paraquat patients.GFR was estimated based on serum cystatin C and creatinine and demonstrated a twofold higher GFR for estimation based on cystatin C estimates than creatinine.

Mentions: Other urinary functional indices such as urinary albumin, and total protein remained steady during the period that serum creatinine rose rapidly (Table 3). Urinary paraquat concentrations were initially high for 24 hours then declined (Table 3). By 24 hours the median paraquat clearance was estimated to be 31 ml/min (IQR 15 to 61), which was slightly higher than the estimated apparent creatinine clearance (Fig 5). Urine output data was available for a subgroup of 12 patients in the AKI group. Two patients in this group who died were anuric, but most had a urine output of greater than 0.75 ml/kg/hour. The median urine output at 24 hours in AKI group was 0.68 (IQR 0.46–1.25) ml/kg/hour, and this value was used to estimate both creatinine and paraquat clearance in patients in whom urine volume data were missing.


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)

Daily GFR estimates in paraquat patients.GFR was estimated based on serum cystatin C and creatinine and demonstrated a twofold higher GFR for estimation based on cystatin C estimates than creatinine.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0122357.g005: Daily GFR estimates in paraquat patients.GFR was estimated based on serum cystatin C and creatinine and demonstrated a twofold higher GFR for estimation based on cystatin C estimates than creatinine.
Mentions: Other urinary functional indices such as urinary albumin, and total protein remained steady during the period that serum creatinine rose rapidly (Table 3). Urinary paraquat concentrations were initially high for 24 hours then declined (Table 3). By 24 hours the median paraquat clearance was estimated to be 31 ml/min (IQR 15 to 61), which was slightly higher than the estimated apparent creatinine clearance (Fig 5). Urine output data was available for a subgroup of 12 patients in the AKI group. Two patients in this group who died were anuric, but most had a urine output of greater than 0.75 ml/kg/hour. The median urine output at 24 hours in AKI group was 0.68 (IQR 0.46–1.25) ml/kg/hour, and this value was used to estimate both creatinine and paraquat clearance in patients in whom urine volume data were missing.

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