Journal of Clinical Apheresis 29:183–186 (2014)
Case Report Hemolytic Uremic Syndrome Associated with Paraquat Intoxication Ha Nee Jang,1 Eun Jin Bae,1 Kyungo Hwang,1 Yeojin Kang,1 Seongeun Yun,1 Hyun Seop Cho,1 Se-Ho Chang,1,2 and Dong Jun Park1,2* 1
Department of Internal Medicine, School of Medicine Gyeongsang University, Jinju, South Korea 2 Institute of Health Science, Gyeongsang National University Hospital, Jinju, South Korea
We report a case of a 66-year-old patient with paraquat intoxication resulting in the requirement for hemoperfusion, hemodialysis, and plasma exchange. His initial serum paraquat level was 0.24 mg/mL (0.0–0.1 mg/mL). Activated charcoal (50 g) was administered orally, and high-dose N-acetylcysteine (150 mg/kg) was administered intravenously. In addition, immediate 4 h hemoperfusion was also performed for three consecutive days after admission. Hemodialysis was started on the 4th day after admission because of uremia. On the 9th day after admission, laboratory findings demonstrated hemolytic uremic syndrome (HUS): microangiopathic hemolytic anemia (MAHA), thrombocytopenia, elevated reticulocyte count, and lactate dehydrogenase (LDH). Plasma exchange was performed three times consecutively. Anemia and thrombocytopenia were improved, and LDH was normalized after plasma exchange. Urine output increased to 2240 mL/day on the 18th day after admission, and hemodialysis was discontinued. He is currently being observed at our follow-up clinic without renal impairment or pulmonary dysfunction for 1.5 years since discharge. We should suspect paraquat-associated HUS when thrombocytopenia and anemia are maintained for a long time after paraquat intoxication. J. Clin. Apheresis C 2013 Wiley Periodicals, Inc. 29:183–186, 2014. V Key words: hemolytic uremic syndrome; acute kidney injury; paraquat; plasma exchange
INTRODUCTION
Hemolytic uremic syndrome (HUS) refers to the triad of a nonimmune (Coombs negative), microangiopathic hemolytic anemia (MAHA), low platelet count, and renal failure [1]. Anemia is usually severe and microangiopathic in nature with fragmented red blood cells (schistocytes) in the peripheral smear, and serum lactate dehydrogenase (LDH) and reticulocytes levels are high. Medication-related MAHA can develop in several clinical conditions. Several drugs including antineoplastic drugs, immunosuppressants, antiplatelet agents, antibiotics, interferon, and nonsteroidal antiinflammatory drugs are associated with HUS (Table I) [1–3]. Intentional or accidental intoxication of paraquat is frequently fatal due to the failure of multiple organs: pulmonary edema, cardiac, renal and hepatic failure, and convulsions due to CNS involvement [4]. Early mortality of paraquat poisoning occurs as a result of vascular collapse, whereas delayed mortality is mainly due to lung fibrosis. Medical management of paraquat ingestion includes prevention of intestinal absorption with activated charcoal and Fuller’s EarthV (Syngenta, Korea), which is used for adsorbent for acute paraquat intoxication, elimination methods such as hemodialysis R
C 2013 Wiley Periodicals, Inc. V
and hemoperfusion, immunosuppression with dexamethasone, cyclophosphamide, and methylprednisolone, and infusion of antioxidants such as acetylcysteine and salicylate [5]. Although several clinical conditions associated with paraquat were reported, no one has reported that paraquat is associated with HUS. We describe a patient with HUS secondary to paraquat intoxication who has completely recovered by three treatment modalities: plasma exchange, hemodialysis, and hemoperfusion. CASE
A 66-year-old man was referred to our emergency room (ER) due to paraquat intoxication. He had been economically distressed and drank alcohol mixed with 10 mL paraquat (20% concentrate) with the intent of *Correspondence to: Dong Jun Park, Department of Internal Medicine, School of Medicine, Gyeongsang University, 92 Chiram-dong, Jinju city. Gyeongsangnam-do, South Korea. E-mail: [email protected] Received 19 March 2013; Accepted 7 November 2013 Published online 25 November 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jca.21310
184
Jang et al.
examination shows normal findings. His extremities did not show pitting edema, cyanosis, or clubbing. He was mildly drowsy, and there were no other neurologic deficits on neurologic examination. A semi-quantitative test (ranged from 0 to 1111) applied for a measure of urine paraquat using bicarbonate and sodium dithionite known as ‘Dithionite method’ [6], which sodium dithionite reduces paraquat to blue radical form in alkaline urine showed two positive results in the initial laboratory findings (Table II). Other initial laboratory test results were as follows: hemoglobin level, 16.8 g/dL; platelet count, 299 3 103/mm3; blood urea nitrogen (BUN) and serum creatinine level, 23 mg/dL and 1.23 mg/dL, respectively; calcium, 8.7 mg/dL; phosphorus, 4.2 mg/dL; total protein, 6.7 g/dL; albumin, 4.2 g/dL; LDH, 199 U/L. His initial serum paraquat level was 0.24 mg/mL (0.0–0.1 mg/mL). There was no evidence of proximal tubular dysfunction such as glycosuria on urinalysis, renal tubular acidosis, and electrolyte abnormalities. According to our protocol for the paraquat intoxication, activated charcoal (50 g) was administrated orally, and high-dose N-acetylcysteine (150 mg/kg) was infused intravenously and immediate 4 h hemoperfusion was performed for three consecutive days after admission. After the second hemoperfusion, thrombocytopenia (14 3 103/mm3) was aggravated, and the platelet concentrate was transfused. The serum level of paraquat was 0.04 mg/mL. Creatinine was increased to 4.71 mg/dL at that time. His urine output was decreased to 200 mL/day, and hemodialysis was started on the 4th day after admission due to volume overload and uremic symptoms. Packed RBCs was transfused on the 4th and 9th days after admission because of aggravation of anemia. We suspected HUS because anemia and thrombocytopenia were still aggravated despite being 7 days after the withdrawal of hemoperfusion. Other etiologies such as infection, drugs, malignancy,
suicide 1 h before. His medical history included hypertension for 5 years. He was a farmer and denied a history of smoking. On physical examination, he had an acute-ill looking appearance, but his vital signs were within normal ranges. His oral mucosa was tinged with a green color, and there was a nasty smell. Abdominal TABLE I. Drugs Associated With the Development of Thrombotic Thrombocytopenic Purpura-Hemolytic Syndrome Antineoplastic drugs Mitomycin C 5-fluorouracil Cytarabine Cisplatin Gemcitabine Immunosuppressants Cyclosporine OKT3 Tacrolimus Antiplatelet drugs Ticlopidine Clopidogrel Dipyridamole Antibiotics Ampicillin Clarithromycin Metronidazole Rifampicin Oxytetracycline Interferon Alpha interferon Alpha 2b interferon Beta interferon Nonsteroidal anti-inflammatory drugs Diclofenac Ketorolac Piroxicam Miscellaneous Quinine Cocaine Heroin Carbon tetrachloride Valacyclovir
TABLE II.
Laboratory Data, Treatment Modalities, and Managements According to Admission Day Day after admission
Serum paraquat level (ug/mL) Urine paraquat screening BUN (mg/dL) Creatinine (mg/dL) LDH (U/L) Hemoglobin (g/dL) Platelet (x103/mm3) Transfusion Treatment modalities
a
a
Initial
1st
2nd
0.24 (11) 23 1.2 199 16.8 299 na HP
na (1) 19 0.85 na 14.2 93 na HP
0.04 na 45.2 4.71 na 11.8 14 PC (x8) HP
a
3rd
4tha
9tha
10tha
11tha
12tha
18tha
0.07 (-) 84 6.9 na 9.1 22 PC (x8) na
na na 117 13.6 na 7.8 67 PRC (x2) HD
na na 63.8 11.7 948 5.4 48 PRC (x2) PE
na na 76 14.71 791 8.7 45 na HD 1 PE
na na 56 11.37 348 8.1 73 na PE
na na 72 13.2 280 8.0 100 na HD
Na Na 34 11.59 225 7.9 168 Na na
HP, hemoperfusion; HD, hemodialysis; PE, plasma exchange; PRC, packed red blood cells; PC, platelet concentrate; na, not-applicable; LDH, lactic dehydrogenase. a All numerical values are just before HP, HD, and PE. Journal of Clinical Apheresis DOI 10.1002/jca
HUS Associated with Paraquat
and other toxins that could induce HUS were not identified. A peripheral blood smear shows more than 10 schistocytes on high field power. A high LDH level (948 U/L) and a high reticulocyte count (5%) were detected, and the creatinine level was 11.7 mg/dL even with hemodialysis (Table II). Prothrombin time and activated partial thromboplastin time were within normal ranges. The patient was diagnosed with HUS, and 3600 mL plasma exchange was prescribed for three consecutive days. Thereafter, the LDH level was decreased to 280 U/L, and the hemoglobin level was maintained without further transfusion. Thrombocytopenia also disappeared after plasma exchange (Table II). Urine output increased to 2240 mL/day on the 18th day after admission, and hemodialysis was discontinued. He was discharged on the 30th day after admission, although it took 5 months for his renal function to fully recover. He is currently being observed at our follow-up clinic without renal impairment or pulmonary dysfunction for 1.5 years since discharge. DISCUSSION
Our case showed that paraquat was associated with HUS. Although he ingested the fatal herbicide, he survived with the help of three modalities: hemoperfusion, hemodialysis, and plasma exchange. Hemoperfusion was performed to remove early rising of plasma paraquat concentration because he visited to our ER just 1 h after intoxication. Hemodialysis was undergone because of progressive azotemia, volume expansion, and uremic symptoms. In addition, this method might be of little help to remove late plasma paraquat secreting from deeper tissue. Plasma exchange was done for the purpose of treatment of HUS associated with paraquat intoxication. Multiple organs, including those of the central nervous system, and the liver, lungs, gastrointestinal (GI) tract, and kidneys, can be affected by paraquat intoxication [4,5]. Early mortality is usually associated with vascular collapse, whereas delayed mortality is mainly due to fatal pulmonary fibrosis. Initial laboratory parameters are related to the prognosis of patients with acute paraquat poisoning [7,8]. Lesser degrees of leukocytosis, acidosis, and renal, hepatic, and pancreatic failure on admission are good prognostic factors of survival after paraquat intoxication [8]. However, the severity of toxic hepatitis following paraquat ingestion was not associated with mortality in a recent retrospective study [9]. Paraquat is toxic to renal proximal tubular cells and can induce acute tubular necrosis, resulting in elevated BUN and creatinine [7,10,11]. Ninety percent of absorbed paraquat is excreted unchanged in urine within 12–24 h after ingestion; thus, additional elimination can be relatively modest [5]. If renal function is
185
well conserved, the removal rate of paraquat by the kidney will be high. Therefore, preservation of renal function will decrease the absorption of paraquat into other organs. It is also suggested that the initial serum creatinine level is one important factor affecting mortality after paraquat intoxication. We initially thought that acute renal failure (ARF) originated from kidney injury by paraquat, and that thrombocytopenia and anemia resulted from hemoperfusion. However, we suspected HUS because of the persistence of severe thrombocytopenia and anemia despite the withdrawal of hemoperfusion. Delayed occurrence of HUS by paraquat might be explained by the toxicokinetics of paraquat in that a small proportion of paraquat distributed into deeper compartments is only slowly released into the plasma and eliminated by the kidney over several days to weeks due to renal failure. Above all, the strong association between HUS and paraquat ingestion was confirmed by the absence of other causes to induce HUS, such as infection, malignancies, other drugs or toxins except for paraquat, improvement of thrombocytopenia and hemolytic anemia, restoration of the serum LDH level, and renal failure after plasma exchange. One report showed that the average peak serum creatinine level was reached on the 5th day after ingestion, and the creatinine level normalized within 3 weeks [11]. However, it took 5 months for our patient’s serum creatinine level to return to normal. This indirectly demonstrates that ARF did not occur only due to direct injury via paraquat, but rather was complicated by other mechanisms including HUS. We have already reported two cases of postoperative thrombocytopenic thrombotic purpura in which time for a full recovery of renal function took 5 months in one case, and renal impairment was persistent in the other case [12]. This also suggests that the ARF in our case was associated with HUS. In conclusion, paraquat is associated with HUS, and plasma exchange may be one appropriate treatment. REFERENCES 1. Ruggenenti P, Noris M, Remuzzi G. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int 2001;60:831–846. 2. Noris M, Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol 2005;16:1035–1050. 3. Medina PJ, Sipols JM, George JN. Drug-associated thrombotic thrombocytopenic purpura -hemolytic uremic syndrome. Curr Opin Hematol 2001;8:286–293. 4. Vale JA, Meredith TH, Buckley BM. Paraquat poisoning: clinical features and immediate general management. Hum Toxicol 1987;6:41–47. 5. Gawarammana IB, Buckley NA. Medical management of paraquat ingestion. Brit J Clin Pharmacol 2010;72:745–757. 6. Goulding R, Volans GN, Come P, Widdop B. Paraquat poisoning. Brit Med J 1976;1:42. Journal of Clinical Apheresis DOI 10.1002/jca
186
Jang et al.
7. Hong SY, Yang DH, Hwang KY. Associations between laboratory parameters and outcome of paraquat poisoning. Toxicol Lett 2000;118:53–59. 8. Lee EY, Hwang KY, Yang JO, Hong SY. Predictors of survival after acute paraquat poisoning. Toxicol Ind Health 2002;18:201–206. 9. Yang CJ, Lin JL, Lin-Tan DT, Weng CH, Hsu CW, Lee SY, Lee SH, Chang CM, Lin WR, Yen TH. Spectrum of toxic hepatitis following intentional paraquat ingestion: analysis of 187 cases. Liver Int 2012;5:1428–1432.
Journal of Clinical Apheresis DOI 10.1002/jca
10. Vaziri ND, Ness RL, Fairshter RD, Smith WR, Rosen SM. Nephrotoxicity of paraquat in man. Arch Intern Med 1979;139: 172–174. 11. Kim SJ, Gil HW, Yang JO, Lee EY, Hong SY. The clinical features of acute kidney injury in patients with acute paraquat intoxication. Nephrol Dial Transpl 2009;24:1226–1232. 12. Lee DW, Seo JW, Cho HS, Kang Y, Kim HJ, Chang SH, Park DJ. Two cases of postoperative thrombotic thrombocytopenic purpura. Ther Apher Dial 2011;15:594–597.
Case Report Hemolytic Uremic Syndrome Associated with Paraquat Intoxication Ha Nee Jang,1 Eun Jin Bae,1 Kyungo Hwang,1 Yeojin Kang,1 Seongeun Yun,1 Hyun Seop Cho,1 Se-Ho Chang,1,2 and Dong Jun Park1,2* 1
Department of Internal Medicine, School of Medicine Gyeongsang University, Jinju, South Korea 2 Institute of Health Science, Gyeongsang National University Hospital, Jinju, South Korea
We report a case of a 66-year-old patient with paraquat intoxication resulting in the requirement for hemoperfusion, hemodialysis, and plasma exchange. His initial serum paraquat level was 0.24 mg/mL (0.0–0.1 mg/mL). Activated charcoal (50 g) was administered orally, and high-dose N-acetylcysteine (150 mg/kg) was administered intravenously. In addition, immediate 4 h hemoperfusion was also performed for three consecutive days after admission. Hemodialysis was started on the 4th day after admission because of uremia. On the 9th day after admission, laboratory findings demonstrated hemolytic uremic syndrome (HUS): microangiopathic hemolytic anemia (MAHA), thrombocytopenia, elevated reticulocyte count, and lactate dehydrogenase (LDH). Plasma exchange was performed three times consecutively. Anemia and thrombocytopenia were improved, and LDH was normalized after plasma exchange. Urine output increased to 2240 mL/day on the 18th day after admission, and hemodialysis was discontinued. He is currently being observed at our follow-up clinic without renal impairment or pulmonary dysfunction for 1.5 years since discharge. We should suspect paraquat-associated HUS when thrombocytopenia and anemia are maintained for a long time after paraquat intoxication. J. Clin. Apheresis C 2013 Wiley Periodicals, Inc. 29:183–186, 2014. V Key words: hemolytic uremic syndrome; acute kidney injury; paraquat; plasma exchange
INTRODUCTION
Hemolytic uremic syndrome (HUS) refers to the triad of a nonimmune (Coombs negative), microangiopathic hemolytic anemia (MAHA), low platelet count, and renal failure [1]. Anemia is usually severe and microangiopathic in nature with fragmented red blood cells (schistocytes) in the peripheral smear, and serum lactate dehydrogenase (LDH) and reticulocytes levels are high. Medication-related MAHA can develop in several clinical conditions. Several drugs including antineoplastic drugs, immunosuppressants, antiplatelet agents, antibiotics, interferon, and nonsteroidal antiinflammatory drugs are associated with HUS (Table I) [1–3]. Intentional or accidental intoxication of paraquat is frequently fatal due to the failure of multiple organs: pulmonary edema, cardiac, renal and hepatic failure, and convulsions due to CNS involvement [4]. Early mortality of paraquat poisoning occurs as a result of vascular collapse, whereas delayed mortality is mainly due to lung fibrosis. Medical management of paraquat ingestion includes prevention of intestinal absorption with activated charcoal and Fuller’s EarthV (Syngenta, Korea), which is used for adsorbent for acute paraquat intoxication, elimination methods such as hemodialysis R
C 2013 Wiley Periodicals, Inc. V
and hemoperfusion, immunosuppression with dexamethasone, cyclophosphamide, and methylprednisolone, and infusion of antioxidants such as acetylcysteine and salicylate [5]. Although several clinical conditions associated with paraquat were reported, no one has reported that paraquat is associated with HUS. We describe a patient with HUS secondary to paraquat intoxication who has completely recovered by three treatment modalities: plasma exchange, hemodialysis, and hemoperfusion. CASE
A 66-year-old man was referred to our emergency room (ER) due to paraquat intoxication. He had been economically distressed and drank alcohol mixed with 10 mL paraquat (20% concentrate) with the intent of *Correspondence to: Dong Jun Park, Department of Internal Medicine, School of Medicine, Gyeongsang University, 92 Chiram-dong, Jinju city. Gyeongsangnam-do, South Korea. E-mail: [email protected] Received 19 March 2013; Accepted 7 November 2013 Published online 25 November 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jca.21310
184
Jang et al.
examination shows normal findings. His extremities did not show pitting edema, cyanosis, or clubbing. He was mildly drowsy, and there were no other neurologic deficits on neurologic examination. A semi-quantitative test (ranged from 0 to 1111) applied for a measure of urine paraquat using bicarbonate and sodium dithionite known as ‘Dithionite method’ [6], which sodium dithionite reduces paraquat to blue radical form in alkaline urine showed two positive results in the initial laboratory findings (Table II). Other initial laboratory test results were as follows: hemoglobin level, 16.8 g/dL; platelet count, 299 3 103/mm3; blood urea nitrogen (BUN) and serum creatinine level, 23 mg/dL and 1.23 mg/dL, respectively; calcium, 8.7 mg/dL; phosphorus, 4.2 mg/dL; total protein, 6.7 g/dL; albumin, 4.2 g/dL; LDH, 199 U/L. His initial serum paraquat level was 0.24 mg/mL (0.0–0.1 mg/mL). There was no evidence of proximal tubular dysfunction such as glycosuria on urinalysis, renal tubular acidosis, and electrolyte abnormalities. According to our protocol for the paraquat intoxication, activated charcoal (50 g) was administrated orally, and high-dose N-acetylcysteine (150 mg/kg) was infused intravenously and immediate 4 h hemoperfusion was performed for three consecutive days after admission. After the second hemoperfusion, thrombocytopenia (14 3 103/mm3) was aggravated, and the platelet concentrate was transfused. The serum level of paraquat was 0.04 mg/mL. Creatinine was increased to 4.71 mg/dL at that time. His urine output was decreased to 200 mL/day, and hemodialysis was started on the 4th day after admission due to volume overload and uremic symptoms. Packed RBCs was transfused on the 4th and 9th days after admission because of aggravation of anemia. We suspected HUS because anemia and thrombocytopenia were still aggravated despite being 7 days after the withdrawal of hemoperfusion. Other etiologies such as infection, drugs, malignancy,
suicide 1 h before. His medical history included hypertension for 5 years. He was a farmer and denied a history of smoking. On physical examination, he had an acute-ill looking appearance, but his vital signs were within normal ranges. His oral mucosa was tinged with a green color, and there was a nasty smell. Abdominal TABLE I. Drugs Associated With the Development of Thrombotic Thrombocytopenic Purpura-Hemolytic Syndrome Antineoplastic drugs Mitomycin C 5-fluorouracil Cytarabine Cisplatin Gemcitabine Immunosuppressants Cyclosporine OKT3 Tacrolimus Antiplatelet drugs Ticlopidine Clopidogrel Dipyridamole Antibiotics Ampicillin Clarithromycin Metronidazole Rifampicin Oxytetracycline Interferon Alpha interferon Alpha 2b interferon Beta interferon Nonsteroidal anti-inflammatory drugs Diclofenac Ketorolac Piroxicam Miscellaneous Quinine Cocaine Heroin Carbon tetrachloride Valacyclovir
TABLE II.
Laboratory Data, Treatment Modalities, and Managements According to Admission Day Day after admission
Serum paraquat level (ug/mL) Urine paraquat screening BUN (mg/dL) Creatinine (mg/dL) LDH (U/L) Hemoglobin (g/dL) Platelet (x103/mm3) Transfusion Treatment modalities
a
a
Initial
1st
2nd
0.24 (11) 23 1.2 199 16.8 299 na HP
na (1) 19 0.85 na 14.2 93 na HP
0.04 na 45.2 4.71 na 11.8 14 PC (x8) HP
a
3rd
4tha
9tha
10tha
11tha
12tha
18tha
0.07 (-) 84 6.9 na 9.1 22 PC (x8) na
na na 117 13.6 na 7.8 67 PRC (x2) HD
na na 63.8 11.7 948 5.4 48 PRC (x2) PE
na na 76 14.71 791 8.7 45 na HD 1 PE
na na 56 11.37 348 8.1 73 na PE
na na 72 13.2 280 8.0 100 na HD
Na Na 34 11.59 225 7.9 168 Na na
HP, hemoperfusion; HD, hemodialysis; PE, plasma exchange; PRC, packed red blood cells; PC, platelet concentrate; na, not-applicable; LDH, lactic dehydrogenase. a All numerical values are just before HP, HD, and PE. Journal of Clinical Apheresis DOI 10.1002/jca
HUS Associated with Paraquat
and other toxins that could induce HUS were not identified. A peripheral blood smear shows more than 10 schistocytes on high field power. A high LDH level (948 U/L) and a high reticulocyte count (5%) were detected, and the creatinine level was 11.7 mg/dL even with hemodialysis (Table II). Prothrombin time and activated partial thromboplastin time were within normal ranges. The patient was diagnosed with HUS, and 3600 mL plasma exchange was prescribed for three consecutive days. Thereafter, the LDH level was decreased to 280 U/L, and the hemoglobin level was maintained without further transfusion. Thrombocytopenia also disappeared after plasma exchange (Table II). Urine output increased to 2240 mL/day on the 18th day after admission, and hemodialysis was discontinued. He was discharged on the 30th day after admission, although it took 5 months for his renal function to fully recover. He is currently being observed at our follow-up clinic without renal impairment or pulmonary dysfunction for 1.5 years since discharge. DISCUSSION
Our case showed that paraquat was associated with HUS. Although he ingested the fatal herbicide, he survived with the help of three modalities: hemoperfusion, hemodialysis, and plasma exchange. Hemoperfusion was performed to remove early rising of plasma paraquat concentration because he visited to our ER just 1 h after intoxication. Hemodialysis was undergone because of progressive azotemia, volume expansion, and uremic symptoms. In addition, this method might be of little help to remove late plasma paraquat secreting from deeper tissue. Plasma exchange was done for the purpose of treatment of HUS associated with paraquat intoxication. Multiple organs, including those of the central nervous system, and the liver, lungs, gastrointestinal (GI) tract, and kidneys, can be affected by paraquat intoxication [4,5]. Early mortality is usually associated with vascular collapse, whereas delayed mortality is mainly due to fatal pulmonary fibrosis. Initial laboratory parameters are related to the prognosis of patients with acute paraquat poisoning [7,8]. Lesser degrees of leukocytosis, acidosis, and renal, hepatic, and pancreatic failure on admission are good prognostic factors of survival after paraquat intoxication [8]. However, the severity of toxic hepatitis following paraquat ingestion was not associated with mortality in a recent retrospective study [9]. Paraquat is toxic to renal proximal tubular cells and can induce acute tubular necrosis, resulting in elevated BUN and creatinine [7,10,11]. Ninety percent of absorbed paraquat is excreted unchanged in urine within 12–24 h after ingestion; thus, additional elimination can be relatively modest [5]. If renal function is
185
well conserved, the removal rate of paraquat by the kidney will be high. Therefore, preservation of renal function will decrease the absorption of paraquat into other organs. It is also suggested that the initial serum creatinine level is one important factor affecting mortality after paraquat intoxication. We initially thought that acute renal failure (ARF) originated from kidney injury by paraquat, and that thrombocytopenia and anemia resulted from hemoperfusion. However, we suspected HUS because of the persistence of severe thrombocytopenia and anemia despite the withdrawal of hemoperfusion. Delayed occurrence of HUS by paraquat might be explained by the toxicokinetics of paraquat in that a small proportion of paraquat distributed into deeper compartments is only slowly released into the plasma and eliminated by the kidney over several days to weeks due to renal failure. Above all, the strong association between HUS and paraquat ingestion was confirmed by the absence of other causes to induce HUS, such as infection, malignancies, other drugs or toxins except for paraquat, improvement of thrombocytopenia and hemolytic anemia, restoration of the serum LDH level, and renal failure after plasma exchange. One report showed that the average peak serum creatinine level was reached on the 5th day after ingestion, and the creatinine level normalized within 3 weeks [11]. However, it took 5 months for our patient’s serum creatinine level to return to normal. This indirectly demonstrates that ARF did not occur only due to direct injury via paraquat, but rather was complicated by other mechanisms including HUS. We have already reported two cases of postoperative thrombocytopenic thrombotic purpura in which time for a full recovery of renal function took 5 months in one case, and renal impairment was persistent in the other case [12]. This also suggests that the ARF in our case was associated with HUS. In conclusion, paraquat is associated with HUS, and plasma exchange may be one appropriate treatment. REFERENCES 1. Ruggenenti P, Noris M, Remuzzi G. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int 2001;60:831–846. 2. Noris M, Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol 2005;16:1035–1050. 3. Medina PJ, Sipols JM, George JN. Drug-associated thrombotic thrombocytopenic purpura -hemolytic uremic syndrome. Curr Opin Hematol 2001;8:286–293. 4. Vale JA, Meredith TH, Buckley BM. Paraquat poisoning: clinical features and immediate general management. Hum Toxicol 1987;6:41–47. 5. Gawarammana IB, Buckley NA. Medical management of paraquat ingestion. Brit J Clin Pharmacol 2010;72:745–757. 6. Goulding R, Volans GN, Come P, Widdop B. Paraquat poisoning. Brit Med J 1976;1:42. Journal of Clinical Apheresis DOI 10.1002/jca
186
Jang et al.
7. Hong SY, Yang DH, Hwang KY. Associations between laboratory parameters and outcome of paraquat poisoning. Toxicol Lett 2000;118:53–59. 8. Lee EY, Hwang KY, Yang JO, Hong SY. Predictors of survival after acute paraquat poisoning. Toxicol Ind Health 2002;18:201–206. 9. Yang CJ, Lin JL, Lin-Tan DT, Weng CH, Hsu CW, Lee SY, Lee SH, Chang CM, Lin WR, Yen TH. Spectrum of toxic hepatitis following intentional paraquat ingestion: analysis of 187 cases. Liver Int 2012;5:1428–1432.
Journal of Clinical Apheresis DOI 10.1002/jca
10. Vaziri ND, Ness RL, Fairshter RD, Smith WR, Rosen SM. Nephrotoxicity of paraquat in man. Arch Intern Med 1979;139: 172–174. 11. Kim SJ, Gil HW, Yang JO, Lee EY, Hong SY. The clinical features of acute kidney injury in patients with acute paraquat intoxication. Nephrol Dial Transpl 2009;24:1226–1232. 12. Lee DW, Seo JW, Cho HS, Kang Y, Kim HJ, Chang SH, Park DJ. Two cases of postoperative thrombotic thrombocytopenic purpura. Ther Apher Dial 2011;15:594–597.
