Gross hematuria after wasp sting is not rare in Asian countries [6, 12, 13]. Current study did a retrospective analysis of 363 cases of wasp sting patients admitted to Suining Central Hospital in Sichuan Province of China. Our research found that 14% of the patients with wasp sting had gross hematuria, and this was only seen in the summer and fall months from July through December. More than half of patients with hematuria (51%) developed oliguria (or anuria). More than 70% of patients with hematuria had AKI, and the fatality (mortality) rate was 25.5%. The poisoning severity score in patients with gross hematuria was significantly higher than that in patients with non-gross hematuria. The poisoning severity score, the season and number of stings turned out to be independent risk factors for gross hematuria in wasp sting patients.
Wasp venom contains a variety of bioactive components, such as enzymes (including phospholipase, hyaluronic acid), amines (including histamine, serotonin, catecholamine), peptides (including wasp venom peptide, wasp kinin)[16]. Phospholipase damages the cell membrane by attacking the phospholipid structure, which has a toxic effect on skeletal muscle and erythrocyte membrane, leading to rhabdomyolysis and intravascular hemolysis[17–19]. Wasp venom peptide can also cause muscle necrosis and cell apoptosis[16, 20]. Venom induced rhabdomyolysis leads to a release of muscle enzymes such as creatine kinase and muscle protein such as myoglobin, free hemoglobin (from red blood cells) in the intravascular circulation[21]. Once in the circulation, these muscle (heme) proteins gets freely filtered through the glomeruli and eventually exceed the tubular reabsorption capacity of renal tubules resulting in gross hematuria[22]. Kidney biopsy study in wasp sting-induced kidney injury has demonstrated deposition of myoglobin and hemoglobin in renal tubules[23–25].
Prior study has shown that gross hematuria associated with wasp sting generally occurs 4–12 hours after sting, and tends to occur earlier than AKI [26]. In our cohort, 14% of wasp sting patients presented with gross hematuria. These patients also had a higher poisoning severity score at the time of admission. The incidence of serious complications such as AKI, MODS, ARDS, and mortality were significantly higher than those reported by Xie [12]. Therefore, gross hematuria can be used as one of the early indicators of severe wasp sting patients and requires active intervention. Multivariate logistic regression analysis showed that the poisoning severity score was an independent risk factor for patients suffering from wasp stings to develop gross hematuria. One point increase in the poisoning severity score correlated with 99.6 times increased risk of developing gross hematuria. The poisoning severity score is widely used in Europe to assess the severity of poisoned patients (including environmental toxins), with simple and accurate characteristics [9, 27]. However, it has not been reported specially for the evaluation of wasp sting patients. ROC curve analysis of poisoning severity score for predicting gross hematuria in wasp sting patients shows that when the poisoning severity score is greater than 1.5, the risk of gross hematuria is significantly increased with high accuracy (AUC = 0.928). In brief, gross hematuria reflects a high poisoning severity score and thus can be used as a surrogate marker of worse clinical outcome following a wasp sting. Meanwhile, the poisoning severity score can be used for early assessment of the severity of wasp sting patients and is worthy of promotion in clinical practice.
In developed countries, wasp stings are mainly manifested in varying degrees of allergic-reactions, therefore their treatment mainly focuses on desensitization and antiallergic treatment[5, 28, 29]. On the other hand, In China, wasp sting patients are mainly characterized by toxic reactions and the main causes of death of wasp sting patients are MODS, ARDS and non-allergic shock[12, 30], which is consistent with our conclusion. Epidemiology in the United States and Sweden shows that wasp stings mostly occur in summer and autumn when the climate is warm, which is related to the increase in the number of wasps and the increase in people's outdoor activities[31, 32]. Multivariate logistic regression analysis also confirmed that gross hematuria is related to the season. In summer and autumn, swarms of wasps are more likely to hurt people. This regional and seasonal difference may be related to the different wasp species in different regions and seasons, and the different components and virulence of wasp venom[17, 33, 34].
The serum creatine kinase, aspartate aminotransferase, lactate dehydrogenase, and indirect bilirubin
of patients with gross hematuria were significantly higher than those of patients with non-gross hematuria on admission and the 2nd-3rd day after admission. Creatine kinase and aspartate aminotransferase are laboratory indicators of rhabdomyolysis [35], while lactate dehydrogenase and indirect bilirubin are laboratory indicators of hemolysis [36], which indicated that patients with gross hematuria experienced more severe and prolonged rhabdomyolysis and intravascular hemolysis. So that patients who develop gross hematuria are likely those who are most severely affected by the venom. While rhabdomyolysis and intravascular hemolysis can cause AKI, the renal injury can be exacerbated in the states of shock [35, 37–39]. However it is rather difficult to explain why patients in the gross hematuria group had developed less shock than in non-gross hematuria group. We further analyzed 51 patients with gross hematuria (Table 5). Serum leucocyte, indirect bilirubin, and creatine kinase had no statistical difference on admission for patients with gross hematuria complicated with AKI (n = 36) and patients without AKI (n = 15). However, serum LDH of patients with gross hematuria complicated with AKI was significantly higher than that of patients without AKI on admission (P = 0.003). This has previously been shown by Li and Zhang that elevated serum LDH is associated with AKI in wasp sting patient population[26, 30]. ROC curve analysis of LDH for predicting AKI in wasp sting patients shows that when LDH was greater than 463.5 U/L, the risk of AKI in wasp sting patients was significantly increased. In the gross hematuria group, AKI group had higher mortality than in the non-AKI group but it was not statistically significant. The serum creatinine of 25 patients with gross hematuria complicated with AKI did not return to normal at discharge (119-925umol/l). According to Zhang's report, 10.7% of patients with wasp sting complicated with AKI will progress to CKD [30]. We have evidence from population based studies that a subset of patients with AKI progress to CKD[40]. It would be therefore be advisable for such patients to be followed in nephrology clinic after their discharge. However, this result may also be related to the short hospitalization time of our patients (average 11 days), because, according to Ambarsari's report, the cure of acute kidney injury after wasp sting takes 3–6 weeks[41].
Table 5
Comparison of gross hematuria without AKI group and gross hematuria with AKI group
Variable | Non-AKI group(n = 15) | AKI group(n = 36) | P |
Age (years) | 64.5 ± 11.4 | 65.4 ± 8.7 | 0.828 |
Gender (M: F) | 5:10 | 20:16 | 0.220 |
Number of stings | 28(20,45) | 30(17,31) | 0.820 |
Interval (hours) | 6(3,24) | 6(4,11.5) | 0.747 |
Poisoning severity score | 1.9 ± 0.6 | 2.25 ± 0.5 | 0.070 |
Hospitalization Days (day) | 9(7,12) | 12.5(2,29) | 0.080 |
serum WBC at admission | 20.5 ± 5.6 | 23.0 ± 8.0 | 0.321 |
serum IBIL at admission | 34.5 ± 19.7 | 50.8 ± 27.7 | 0.062 |
serum CK at admission | 4113.4 ± 6270.1 | 5678.4 ± 9786.1 | 0.602 |
serum LDH at admission | 864.1 ± 366.3 | 1854.0 ± 1610.2 | 0.003 |
serum CREA at admission | 66.6 ± 14.4 | 186.4 ± 203.1 | < 0.001 |
serum CREA at discharge | 61.4 ± 15.3 | 316.5 ± 248.8 | < 0.001 |
Shock n (%) | 0(0) | 1(2.8) | 1.000 |
Rhabdomyolysis n (%) | 14(93.3) | 36(100) | 0.294 |
Hemolysis n (%) | 12(80) | 34(94.4) | 0.144 |
Oliguria or anuria n (%) | 0(0) | 26(72.2) | < 0.001 |
Dialysis n (%) | 8(53.3) | 32(88.9) | 0.009 |
MODS n (%) | 12(80) | 36(100) | 0.022 |
ARDS n (%) | 0(0) | 13(36.1) | 0.006 |
ICU n (%) | 1(6.7) | 6(16.7) | 0.658 |
Death n (%) | 2(13.3) | 11(30.6) | 0.297 |
Note: WBC is a shorthand for Leukocyte, IBIL is a shorthand for Indirect bilirubin, CK is a shorthand for Creatine kinase, LDH is a shorthand for Lactate dehydrogenase, CREA is a shorthand for Creatinine |
Our research also has limitations. Ours is a retrospective study and hence there may be selection bias in addition to possible confounding. Study comes from a single center and we did not have complete information such as wasp species, sting site, prognosis and follow-up of patients with AKI.
To our knowledge, this is the largest study in terms of numbers to study this phenomenon. We also had an extensive biochemical and clinical data available for our cohort. Added to this is the use of multivariate logistic regression analysis and ROC curves to study the association.
In conclusion, the poisoning severity score can be used for early assessment of the severity of wasp sting patients. Gross hematuria is one of the early but serious markers of adverse outcomes in patients with wasp sting and hence should alert clinicians about more aggressive and closer monitoring of such patients.