Sei sulla pagina 1di 7

CJASN ePress. Published on September 5, 2013 as doi: 10.2215/CJN.

12081112
Article

Recovery from AKI Following Multiple Wasp Stings: A


Case Series
Ling Zhang,* Yingying Yang,* Yi Tang,* Yuliang Zhao,* Yu Cao,† Baihai Su,* and Ping Fu*

Summary
Background and objective To observe the outcomes of AKI following multiple wasp stings.
*Division of
Design, setting, participants, & measurements Eighty-one patients (mean age 6 SD, 45.5614.7 years; 55 men and Nephrology and
26 women; mean Acute Physiology and Chronic Health Evaluation II score, 16.8562.78) with AKI following †
Division of
multiple wasp stings between 1997 and 2011 were retrospectively analyzed. Data on their demographic char- Emergency, West
acteristics, initial modalities of renal replacement therapy (RRT), urine output, serum creatinine, bilirubin, China Hospital of
myoglobin, and other variables were collected. Renal outcomes included complete recovery of kidney function, Sichuan University,
Sichuan, Chengdu,
CKD, and death. Subgroup analysis was performed according to initial modality of RRT in the first 48 hours, China
including continuous veno-venous hemofiltration (CVVH), intermittent hemodialysis (IHD), and CVVH plus
plasma exchange (PE). Correspondence:
Dr. Fu Ping, Division
Results Of the 75 patients available for follow-up, 7 (9.3%) died, and 8 (10.7%, all in the IHD group) developed of Nephrology, West
CKD. The average RRT time was 18.268.4 days, and the average kidney function recovery time was 36.0 (29.0, China Hospital of
Sichuan University,
41.0) days. Subgroup analysis showed no difference in the mortality rates between the CVVH, CVVH + PE, and No. 37, Guoxue Alley,
IHD groups (8.0%, 7.1%, and 11.1%, respectively; P.0.99). The recovery time for kidney function was signifi- Chengdu, Sichuan
cantly shorter in the CVVH and CVVH + PE groups than in the IHD group (31.968.5 days, 28.669.4 days, and Province, China.
41.668.1 days, respectively; P,0.001). Email: fupinghx@163.
com

Conclusions This is a large case series report on the outcomes of patients with AKI following multiple wasp stings.
Most patients survived with complete recovery of their kidney function. Despite the lack of difference in
mortality rates, the patients who began RRT with CVVH and CVVH + PE experienced a better and more rapid
recovery of kidney function than those initiated with IHD.
Clin J Am Soc Nephrol 8: ccc–ccc, 2013. doi: 10.2215/CJN.12081112

Introduction on the differing modalities of renal replacement ther-


Wasps and bees are members of the order Hymenop- apy (RRT) in these patients. In this study, we ana-
tera (1). Wasp and bee stings are associated with a lyzed patients with multiple wasp stings at our
wide variety of reactions, ranging from mild local hospital during a 15-year period who were treated
reactions (such as edema, erythema, and urticaria) with IHD, continuous veno-venous hemofiltration
to fatal systemic complications (such as anaphylactic (CVVH), or plasma exchange (PE) to observe the out-
shock, rhabdomyolysis, AKI, myocardial infarction, comes of AKI following multiple wasp stings.
acute hepatic failure, and encephalitis) (2–5). AKI is
usually caused by intravascular hemolysis, rhabdo-
myolysis, shock, and the direct toxic effects of the Materials and Methods
venom; the triad of AKI, hemolysis, and rhabdomyol- Patients
ysis often occurs in patients subjected to multiple Data from 103 patients with multiple wasp stings
wasp or bee stings (6). Renal biopsy usually reveals (.50 stings) admitted to West China Hospital of Si-
acute tubular necrosis (5,6), as well as occasional chuan University between 1997 and 2011 were in-
acute interstitial nephritis (7). More than half of the cluded in our analysis. None of the patients had a
victims who experience multiple wasp or bee stings history of CKD. The diagnosis and staging of AKI
develop AKI, and most of these patients require in- were determined according to the 2012 Kidney Dis-
termittent hemodialysis (IHD) or peritoneal dialysis ease: Improving Global Outcomes guidelines (11).
(PD) (4,8–10). The mortality rate of patients who ex- Among the 103 patients, 81 (78.6%) developed oliguric
perience AKI due to wasp stings has been reported to AKI and received RRT. The clinical course and renal
be as high as 25% (6). Few large case series have ad- outcomes of these 81 patients were observed; subgroup
dressed the outcomes of wasp or bee sting–induced analysis was performed according to the initial modal-
AKI, and to our knowledge no studies have focused ities of RRT in the first 48 hours.

www.cjasn.org Vol 8 November, 2013 Copyright © 2013 by the American Society of Nephrology 1
2 Clinical Journal of the American Society of Nephrology

Data Collection were lost to follow-up within 3 months from AKI onset.
Patient demographic characteristics, including age, sex, These patients still had impaired kidney function at their
disease history, and RRT modality administered, were re- last follow-up, and the final outcomes were unknown.
corded. Important measures, such as mean arterial pres- Twenty patients (24.7%) started RRT at AKI stage 2; 61
sure, urine output, serum creatinine, creatine kinase, lactate patients (75.3%) at AKI stage 3; and none at AKI stage 1.
dehydrogenase, total bilirubin, myoglobin, electrolytes, The important laboratory measures of these patients are
and adverse events, were collected. listed in Table 1.

Observation of Clinical Course and Renal Outcomes General Therapies


Patients were followed up for at least 3 months. Renal Local wounds were washed with normal saline and
outcomes included a complete recovery of kidney function, underwent hydropathic compress protection. Nutrition
CKD, and death. Complete recovery of kidney function support and short-term glucocorticoids were also admin-
was defined as a decrease in the creatinine level to within a istered. Blood transfusions were performed as necessary.
normal range with normal urine output. CKD was defined
as an estimated GFR of ,60 ml/min per 1.73 m2 or the
occurrence of albuminuria 3 months after the onset of AKI, Modalities of RRT and Subgroup Analysis
ESRD was defined as the requirement of maintenance di- According to the initial RRT modality received, the pa-
alysis 3 months after the onset of AKI, and CKD staging tients were divided into three groups. (1) CVVH group:
was performed according to the 2002 Kidney Disease Out- CVVH was performed (B. Braun Diapact, Diacap Acute M,
comes Quality Initiative guidelines (12,13). The recovery 1.5 m2) using predilution bicarbonate replacement fluid
time of kidney function, causes of death, and changes in at a rate of 30–35 ml/kg per hour with a blood flow rate
important laboratory measures were also recorded. of 150–200 ml/min. Citrate was considered the first choice
for anticoagulation, and low-molecular-weight heparin
was used as an alternative when patients had contraindi-
Indication of RRT cations to citrate, such as severe liver dysfunction or per-
Patients were treated with RRT when they had AKI with
sistent poor tissue perfusion. CVVH was performed for at
oliguria (urine output ,100 ml in a 6-hour period or ,400 ml
least 48 hours and then was replaced by IHD when the
per day) or complicated by hyperkalemia, metabolic acidosis,
condition of the patient became stable. (2) CVVH + PE
or acute pulmonary edema.
group: In addition to the CVVH and IHD therapies re-
Available RRT modalities included IHD, CVVH, and PE.
ceived by the CVVH group, the CVVH + PE group re-
Patients received different RRT modalities mainly on the
ceived PE once daily on day 1 and day 2 with a 2000- to
basis of illness severity. Compared with IHD, CVVH was
2500-ml exchange volume each time using fresh-frozen
always performed on patients with more severe symptoms,
plasma. (3) IHD group: IHD was performed (Gambro
especially when the AKI was complicated by multiple organ
AK-200 or B. Braun Dialog) three times per week for
dysfunctional syndromes (MODS). PE was considered
4 hours per session using low-molecular-weight heparin
when patients had severe hemolysis and rhabdomyolysis.
or heparin for anticoagulation with a blood flow rate of
RRT was stopped when urine output was .1500 ml/d
200–250 ml/min and a Kt/V ratio of 1.2–1.4.
without fluid overload and the serum creatinine level
The subgroup analysis showed no significant differences
was ,3 mg/dl.
between the treatment groups with regard to mean arterial
pressure, hemoglobin, lactate dehydrogenase, APACHE II
Statistical Analyses score, or AKI stage at the baseline readings, but there were
Continuous variables were expressed as mean 6 SD or significant differences in the creatinine, total bilirubin,
as the median (25th and 75th percentiles), as appropriate. myoglobulin, and creatine kinase levels, as well as in the
Subgroup analysis was conducted according to the initial proportion of patients with MODS, between the different
RRT modalities. One-way ANOVA, the Scheffe test, or the treatment groups (Table 1). The average treatment times for
Kruskal-Wallis test was used to make comparisons be- the CVVH and CVVH + PE groups were 51.4618.8 and
tween groups. Categorical variables were expressed as 49.6622.1 hours, respectively (P=0.37). The IHD group re-
proportions and were compared using the chi-squared ceived an average of 12.468.4 dialysis sessions.
test or Fisher exact test. P values , 0.05 were considered
to represent statistically significant differences. All statis-
tical analyses were conducted using SPSS software, ver- Survival and Recovery of Kidney Function
Of the 75 patients available for follow-up, 7 patients died,
sion 20.0 (SPSS Inc., Chicago, IL).
which corresponded to a mortality rate of 9.3%; the causes
of death were acute pulmonary edema (n=3), MODS (n=3),
Results and acute digestive tract hemorrhage (n=1). Kidney func-
General Characteristics tion completely recovered in 60 patients (80.0%). Of the 8
Of the 103 patients with multiple wasp stings, 87 (84.5%) patients (10.7%) in the IHD group who developed CKD, 3
had AKI, and 60 (68.9%) presented with MODS complica- were in CKD stage 2, 3 were in CKD stage 3, and 2 devel-
tions. Of the patients who developed AKI, 6 (6.9%) had oped ESRD. Two of the patients with CKD stage 2–3 pre-
nonoliguric AKI and recovered without RRT. Of the 81 sented mild proteinuria (0.5 and 0.7 g/24 hours). The
patients (93.1%; Acute Physiology and Chronic Health average time required for RRT was 18.268.4 days, and it
Evaluation [APACHE] II score, 16.8562.78) who received took an average of 36.0 (29.0, 41.0) days for patients to
RRT, 6 (2 in the CVVH group and 4 in the IHD group) recover kidney function (Table 2).
Clin J Am Soc Nephrol 8: ccc–ccc, November, 2013 AKI Following Multiple Wasp Stings, Zhang et al. 3

Table 1. Demographic and clinical characteristics of patients with AKI at baseline

Total IHD CVVH CVVH + PE


Variable P Value
(n=81) (n=40) (n=27) (n=14)

Age (yr) 45.5614.7 42.6615.7 49.1613.5 47.1613.1 0.19


Men/women 55/26 29/11 17/10 9/5 0.69
Hypertension 7 3 3 1 0.87
Diabetes 6 3 1 2 0.38
MAP (mmHg) 98.9616.6 96.7615.4 98.6618.2 105.9615.9 0.20
Hemoglobin (g/dl) 10.0762.11 9.8561.73 10.4762.49 9.9362.36 0.48
White blood cell count 25.8768.12 25.1468.64 26.8268.31 26.1366.34 0.71
(3103/ml)
Creatinine (mg/dl) 3.2760.94 2.9860.76 3.6061.04a 3.3861.00 0.02
Total bilirubin (mg/dl) 4.5962.87 2.8161.47 4.9862.06a 8.8962.37a,b ,0.001
Alanine aminotransferase (U/L) 729.46629.1 629.26533.1 816.46781.9 847.66546.4 0.37
Myoglobulin (U/L) 1678368794 1231966149 1942868525a 2443568844a ,0.001
Creatine kinase (U/L) 20080610821 1470068121 2280469226a 30201611732a ,0.001
LDH (U/L) 537162665 503962642 569862783 569162568 0.55
APACHE II score 16.8562.78 16.3862.36 17.0063.33 17.9362.56 0.19
MODS 60/81 25/40 21/27 14/14a 0.01
Time from sting to RRT (h) 56.7628.4 61.1624.9 57.8631.4 42.57629.5 0.11
Time from admission to RRT (h) 8.964.9 8.364.8 9.764.6 9.265.2 0.49
AKI stage (stage 2/stage 3) (n/n) 20/61 13/27 3/24 4/10 0.12

Comparisons among the three groups with respect to age, MAP, hemoglobin, white blood cell count, creatinine, total bilirubin, alanine
aminotransferase, myoglobulin, creatine kinase, LDH, APACHE II score, time from sting to RRT, and time from admission to RRT were
performed using ANOVA. Comparisons among the three groups based on sex, hypertension, diabetes, MODS, and AKI stage were
performed using the Fisher exact test. Pairwise comparisons among the three groups with respect to creatinine, total bilirubin, my-
oglobulin, and creatine kinase levels were performed using the Scheffe test. Pairwise comparisons among the three groups with respect
to the proportion of patients with MODS were performed using the chi-square test. IHD, intermittent hemodialysis; CVVH, continuous
veno-venous hemofiltration; PE, plasma exchange; MAP, mean arterial pressure; LDH, lactate dehydrogenase; APACHE II, Acute
Physiology and Chronic Health Evaluation II; MODS, multiple organ dysfunction syndrome; RRT, renal replacement therapy.
a
Significant differences when compared to IHD group.
b
Significant differences when compared to CVVH group.

Subgroup analysis showed no significant differences in on the 3rd and 7th days after AKI onset (P,0.001) (Table 3).
the mortality rates among the three treatment groups (IHD Additionally, the creatinine level rebounded on the 7th
group: 11.1%; CVVH group: 8.0%; CVVH + PE group: 7.1%; day after AKI onset in the IHD group (P=0.002) (Table
P.0.99). However, compared with the CVVH and CVVH + 3). Although the three groups did not significantly differ
PE groups, the IHD group experienced a lower rate of com- in plasma creatine kinase, myoglobulin, and total bilirubin
plete recovery of kidney function (IHD group: 66.7%; CVVH levels on the 7th day after AKI onset (all P.0.05), these
group: 92.0%; CVVH + PE group: 92.9%; P=0.02) (Table 2). values decreased at a faster rate in the CVVH and CVVH +
By the 90th day after the onset of AKI, kidney function PE groups within the first 3 days of AKI onset relative to
recovered completely in all of the survivors in the CVVH the respective baseline levels (Figure 1). Furthermore, total
and CVVH + PE groups. However, in the IHD group, bilirubin decreased more in the CVVH + PE group than in
8 patients (22.2%) developed CKD. Additionally, the total the CVVH group (P=0.007).
time for RRT treatment was significantly shorter in the
CVVH and CVVH + PE groups than in the IHD group (IHD Adverse Events
group: 22.667.0 days; CVVH group: 14.467.2 days; The main complications associated with RRT were ar-
CVVH + PE group: 13.768.3 days; P,0.001). Similarly, rhythmia, hypotension, and bleeding. No patients required
the time to recovery of kidney function was significantly vasopressors before or during RRT.
shorter in the CVVH and CVVH + PE groups (IHD group: The IHD group had a higher incidence of hypotension
39.0 (36.8, 43.0) days; CVVH group: 32.0 (25.0, 38.0) days; than the other two groups (IHD group, 9 of 40; CVVH
CVVH + PE group: 25.0 (19.5, 32.0) days; P,0.001) (Table 2). group, 0 of 27; CVVH + PE group, 0 of 14; P=0.005). Pa-
tients in the CVVH group were most likely to have hypo-
Changes in Biochemical Measures phosphatemia (IHD group, 0 of 40; CVVH group, 7 of 27;
Serum levels of total bilirubin, myoglobulin, and creatine CVVH + PE group, 2 of 14; P,0.001), but this symptom
kinase decreased steadily through the first 7 days of the improved without additional interventions after the ces-
treatment course, and the serum level of creatinine fluctu- sation of CVVH. The three groups did not significantly
ated (Figure 1). differ regarding other adverse events, such as arrhythmia,
Subgroup analysis showed that the IHD group had a hypertension, catheter-related infections, and bleeding
higher level of serum creatinine than the other two groups episodes.
4 Clinical Journal of the American Society of Nephrology

Table 2. Primary outcomes of patients overall and in the different groups

Total IHD CVVH CVVH + PE


Variable P Value
(n=75) (n=36) (n=25) (n=14)

Complete recovery (n) 60 24 23 13 0.02


CKD (n) 8 8 0 0 —
ESRD (n) 2 2 0 0 —
Death (n) 7 4 2 1 —
Mortality rate (%) 9.3 11.1 8.0 7.1 1.0
Required RRT time (d) 18.268.4 22.667.0 14.467.2a 13.768.3a ,0.001
Recovery of kidney 36.0 (29.0, 41.0) 39.0 (36.8, 43.0)a,b 32.0 (25.0, 38.0)a 25.0 (19.5, 32.0)a ,0.001
function (d)

Values expressed with a plus/minus sign are the mean 6 SD; data in parentheses are interquartile ranges. Comparisons among the
three groups with respect to the complete recovery rate and the mortality rate were performed using the Fisher exact test. Comparisons
among the three groups with respect to the time of requiring RRT was performed using the ANOVA test. Pairwise comparisons of the
three groups were performed using the Scheffe test. Comparisons among the three groups as well as pairwise comparisons with respect
to the time of recovery of kidney function were performed using the Kruskal-Wallis test. IHD, intermittent hemodialysis; CVVH,
continuous veno-venous hemofiltration; PE, plasma exchange; RRT, renal replacement therapy.
a
Significant differences when compared to IHD group.
b
Significant differences when compared to CVVH group.

Figure 1. | Changes in the biochemical measures in the three groups. (A) Serum creatinine (mg/dl), (B) total bilirubin (mg/dl), (C) myoglobin (U/L),
(D) creatine kinase (U/L). Conversion factors for units: creatinine in mg/dl to mmol/L, 388.4; total bilirubin in mg/dl to mmol/L, 317.1. CVVH,
continuous veno-venous hemofiltration; IHD, intermittent hemodialysis; PE, plasma exchange.

Discussion to achieve complete kidney recovery; however, 9.3% of


This was a large case series report on the outcomes of them died, and 10.7% of them developed CKD.
AKI patients following multiple wasp stings. We found Apoidea (bees), Vespoidea (wasps, hornets, and yellow
that the incidence of AKI after multiple wasp stings was as jackets), and Formicidae (ants) are groups of the order
high as 84.5%. Eighty percent of the AKI patients were able Hymenoptera (1). Hymenoptera venoms are complex
Clin J Am Soc Nephrol 8: ccc–ccc, November, 2013 AKI Following Multiple Wasp Stings, Zhang et al. 5

Table 3. Percentage decrease in the biochemical measures in the first 3 days

Variable Total (n=81) IHD (n=40) CVVH (n=27) CVVH + PE (n=14) P Value

Creatinine (%) 3.6 224.1 24.8 19.2 ,0.001


(230.9, 24.5) (256.6, 3.4) (2.6, 50.5)a (3.5, 39.8)a
Total bilirubin (%) 40.3 12.1 40.7 60.6 ,0.001
(21.4, 54.8) (225.6, 48.6) (26.6, 54.7)a (48.5, 67.6)a,b
Myoglobulin (%) 48.1 36.9 49.5 61.1 ,0.001
(29.2, 60.3) (14.8, 50.2) (42.9, 61.4)a (48.1, 71.3)a
Creatine kinase (%) 46.0 25.1 55.3 55.3 ,0.001
(20.8, 57.7) (250.0, 47.7) (33.3, 68.6)a (45.5, 66.8)a

Data are expressed as the medians (25th, 75th percentile) and were compared between groups using the Kruskal-Wallis test. IHD,
intermittent hemodialysis; CVVH, continuous veno-venous hemofiltration; PE, plasma exchange.
a
Significant differences when compared to IHD group.
b
Significant differences when compared to CVVH group.

mixtures of biologically active components primarily com- AKI in our center. However, in some cases, patients, par-
posed of peptides, enzymes, and amines. Bee venom, ticularly children, received PD and recovered completely
which has been studied to a greater extent than the venom (8,24). Because the number of patients with wasp sting–
of other species within the order Hymenoptera, contains induced AKI who were receiving PD was limited, we sus-
melittin, phospholipase A2 (PLA2), mast cell–degranulating pect that the selection of patients and the experience of
peptide (peptide 401), hyaluronidase, and apamin, among clinical centers could have significantly influenced the
other constituents (1). Melittin, which makes up approxi- outcomes of these cases. In general, the effect of PD in
mately 50% of the entire bee venom mixture (14), power- severe AKI remains controversial (27), and the role of
fully disrupts cell membranes and has direct toxic effects PD in patients with multiple wasp stings will require fur-
on renal tubular cells of the host (15–17). Wasp venom ther investigation. In this study, we found that .80% of
does not contain melittin. Instead, wasp venom contains patients with multiple wasp stings developed AKI, .90%
antigen 5 as the main allergen; however, the bioactivity of whom required RRT; these results are consistent with
of antigen 5 has not yet been fully determined (1). Vic- those of recent case studies (9,10). However, we reported a
tims attacked by wasps or bees can have mild local or mortality rate of 9.3%, which is low relative to the 18.0%
regional reactions (e.g., swelling, urticaria, erythema, and (2 of 11 patients) (9) and 16.3% (7 of 43 patients) (10) rates
pain), as well as severe systemic anaphylactic responses. reported in earlier studies. Although the number of pa-
A description of the stinging insects by their victims, the tients included in these studies was limited and some
circumstances surrounding the sting episode, and the lo- patients were stung by different species of wasps and
cal signs of stings can be helpful in differentiating be- bees, making direct comparisons of the severity of sick-
tween wasp and bee stings (Table 4) (18–20). Patients ness more difficult, we believe that the lower mortality
with multiple wasp or bee stings could progress to AKI rate in our study could be partially related to the more
or even MODS. Rhabdomyolysis, hemolysis, and cardio- diversified RRT modalities used.
vascular depression caused by venom and direct neph- Mortality did not significantly differ among the IHD,
rotoxicity are considered the main mechanisms of bee CVVH, and CVVH + PE groups, which could be partially
venom–induced AKI (15,21–23). due to the limited number of patients. Although there
In this retrospective study, we found that the mortality were no significant differences in the APACHE II scores
rate of AKI following multiple wasp stings was 9.3%, between any of the groups, patients who received CVVH
which is lower than that of previous reports, in which or CVVH + PE presented higher levels of total bilirubin,
patients with AKI following multiple wasp or bee stings myoglobulin, and creatine kinase, which indicated that
were treated with IHD and PD and had a mortality rate these patients experienced more severe rhabdomyolysis
between 16% and 25% (6,9,10). Previous studies also and hemolysis. In addition, there were larger proportions
showed that, among the patients who survived, 1–3 of patients with MODS in the CVVH and CVVH + PE
months was required to recover full kidney function groups than in the IHD group. Notably, the patients who
(4,6,8–10,24–26). In our study, the average recovery developed CKD all belonged to the IHD group (8 of 36
time of kidney function was shorter in the CVVH or [22.2%]). A previous study (10) that included 43 patients
CVVH + PE group than in IHD group, and we believe with AKI after being stung by Africanized bees showed
that this might be partially related to the different RRT that only 41.7% of patients had normal kidney function
modalities used. at their last follow-up (average duration of follow-up,
In fact, six adult victims of wasp stings who were 25.2618.3 days). In our study, 66.7% of the patients in
admitted to our hospital between 1995 and 1996 received the IHD group achieved complete kidney function recov-
PD treatment. Of these patients, one did not return for follow- ery by the 90th day of follow-up, but these patients
up, two died, and three developed ESRD. PD was sub- experienced a much longer recovery time for kidney
sequently discontinued in patients with wasp sting–induced function than those in the CVVH and CVVH + PE
6 Clinical Journal of the American Society of Nephrology

Table 4. Differences between wasp and bee stings

Variable Bees Wasps

Body shape Fuzzy Smooth


Food Nectar and pollen Insects and sweet substances (e.g., sap, nectar,
soft drinks, and cans)
Circumstances of sting Usually near flowers or a beehive Near, for example, open soft drink cans; when
incidents performing outdoor activities that disturb
their nests
Type of sting Sting only once, usually with a Sting repeatedly, normally without a stinger
stinger (with barbs) in the skin (without barbs) in the skin
Medically important Melittin (2.8 kD) Antigen 5 (23 kD)
components in venom PLA2 (14.5 kD) PLA1 (34 kD)
(references 30–32) Hyaluronidase (39 kD) Hyaluronidase (38 kD)
Acid phosphatase (43 kD)

PLA2, phospholipase A2; PLA1, phospholipase A1.

groups. Therefore, patients administered continuous RRT agents, and the inflammation mediators in circulating
seemed to have a better and more rapid kidney recovery blood (36), but future studies should explore the optimal
than patients who received IHD. The reasons for this ob- initiation time and frequency of PE.
servation are unclear, but we think that this difference Some studies have shown that earlier RRT interventions
could be partially related to the more stable internal en- could improve the outcomes of patients with severe AKI
vironment and smoother fluid balance control experi- (37–39). However, in our study, 75.3% of the patients in
enced by the patients who were administered our study did not receive RRT until they reached stage 3
continuous RRT. Patients in the IHD group received di- AKI. This delay in the initiation of RRT may arise par-
alysis three times per week, and these patients experi- tially because most wasp attacks occurred in the country-
enced more episodes of intradialytic hypotension, side or mountainous areas, requiring extra time for the
which could have induced kidney ischemia. transport of patients from local clinics to hospitals capa-
Moreover, hemolysis and rhabdomyolysis play a pivotal ble of performing RRT. We also noted that all 7 patients
role in multiple wasp or bee sting–induced AKI. Compared who did not survive died within 72 hours after admis-
with IHD, CVVH and/or PE may have provided a more sion, which may suggest that earlier RRT intervention
effective clearance of some toxins with a large molecular could be beneficial for AKI patients following multiple
weight. Myoglobin (17,800 D), the “secondary toxin” pro- stings. However, this observation needs to be confirmed
duced by rhabdomyolysis following wasp and bee stings, in future studies.
could be cleared by CVVH, which has sieving coefficients This study has some limitations. The study was a retro-
that range from 0.23 to 0.60 (28,29). Most of the compo- spective analysis, and the number of patients was limited.
nents of wasp and bee venoms are also large molecules, The selection of RRT modalities was generally dependent
which makes these components subject to clearance by on the experience of the physician in charge and was based
CVVH (Table 4) (30). The main component of bee venom on the general condition of the patient and various lab-
is melittin, which is a 2800-D water-soluble polypeptide, oratory measures. Six patients were lost to follow-up in this
each peptide of which consists of 26 amino acid residues study, which might, to some extent, overestimate the sur-
(31), and PLA2, which has a molecular mass of 14,500 D vival rate. However, the comparison of complete recovery
and is also water soluble (32). Antigen 5 and phospholi- of kidney function rate would probably still show a trend in
pase A1 (PLA1), the chief components of wasp venom, favor of the CVVH or CVVH + PE group even if none the
have even larger molecular masses of 23,000 and 43,000 six patients recovered kidney function. Furthermore, the
D, respectively (30). Theoretically, CVVH could remove selection of RRT modality could have been influenced by
these toxins more effectively than conventional 4-hour, many factors beyond the severity of patient illness, such as
standard-flux IHD. Unfortunately, our study provides the financial status of patients. Further larger prospective
no direct evidence regarding the effect of RRT on remov- studies are needed to confirm our results.
ing wasp or bee venom components, and future studies In conclusion, this is a large case series report on the out-
should investigate this possibility. comes of patients with AKI following multiple wasp stings.
Although the mechanism remains unclear, myoglobulin, Most patients survived with complete recovery of their
creatine kinase, and total bilirubin decreased faster in the kidney function. Despite the lack of difference in mortality
CVVH group, and this effect appears to have been exag- rates, the patients initiated with CVVH and CVVH + PE ex-
gerated by PE. PE has proven effective in patients who have perienced a better and more rapid recovery of kidney func-
ingested poison and been bitten by a snake (33), but the tion compared with those initiated with IHD.
evidence of the efficacy of PE in patients with wasp or bee
stings is limited (34,35). We believe that PE is advantageous Disclosures
in clearing the venom components, the secondary toxic None.
Clin J Am Soc Nephrol 8: ccc–ccc, November, 2013 AKI Following Multiple Wasp Stings, Zhang et al. 7

References 23. Kang HS, Kim SJ, Lee MY, Jeon SH, Kim SZ, Kim JS: The cardio-
1. Fitzgerald KT, Flood AA: Hymenoptera stings. Clin Tech Small vascular depression caused by bee venom in Sprague-Dawley
Anim Pract 21: 194–204, 2006 rats associated with a decrease of developed pressure in the left
2. Lin CJ, Wu CJ, Chen HH, Lin HC: Multiorgan failure following ventricular and the ratio of ionized calcium/ionized magnesium.
mass wasp stings. South Med J 104: 378–379, 2011 Am J Chin Med 36: 505–516, 2008
3. Roy M, Chatterjee M, Deb S, Pandit N: Encephalitis following 24. Singh LR, Singh YT, Singh S, Singh NSK, Sharma LR: Acute renal
wasp sting. Indian J Pediatr 77: 1193–1194, 2010 failure in a child following multiple wasp stings. Indian J Nephrol
4. Xuan BH, Mai HL, Thi TX, Thi MT, Nguyen HN, Rabenou RA: S 15: 95–97, 2005
warming hornet attacks: Shock and acute kidney injury—a large 25. Atmaram VP, Mathew A, Kurian G, Unni VN: Acute renal failure
case series from Vietnam. Nephrol Dial Transplant 25: 1146– following multiple wasp stings. Indian J Nephrol. 15: 30–32,
1150, 2010 2005
5. Zhang L, Tang Y, Liu F, Shi YY, Cao Y, Xu H, Fu P: Multiple organ 26. Bourgain C, Pauti MD, Fillastre JP, Godin M, François A, Leroy JP,
dysfunction syndrome due to massive wasp stings: An autopsy Droy JM, Klotz F: [Massive poisoning by African bee stings].
case report. Chin Med J (Engl) 125: 2070–2072, 2012 Presse Med 27: 1099–1101, 1998
6. Thiruventhiran T, Goh BL, Leong CL, Cheah PL, Looi LM, Tan SY: 27. Ponce D, Balbi AL, Amerling R: Advances in peritoneal dialysis in
Acute renal failure following multiple wasp stings. Nephrol Dial acute kidney injury. Blood Purif 34: 107–116, 2012
Transplant 14: 214–217, 1999 28. Zhang L, Kang Y, Fu P, Cao Y, Shi Y, Liu F, Hu Z, Su B, Tang W, Qin
7. Chao YW, Yang AH, Ng YY, Yang WC: Acute interstitial nephritis W: Myoglobin clearance by continuous venous-venous haemo-
and pigmented tubulopathy in a patient after wasp stings. Am J filtration in rhabdomyolysis with acute kidney injury: A case
Kidney Dis 43: e15–e19, 2004 series. Injury 43: 619–623, 2012
8. Bresolin NL, Carvalho LC, Goes EC, Fernandes R, Barotto AM: 29. Naka T, Jones D, Baldwin I, Fealy N, Bates S, Goehl H, Morgera S,
Acute renal failure following massive attack by Africanized bee Neumayer HH, Bellomo R: Myoglobin clearance by super high-
stings. Pediatr Nephrol 17: 625–627, 2002 flux hemofiltration in a case of severe rhabdomyolysis: A case
9. Paudel B, Paudel K: A study of wasp bites in a tertiary hospital of report. Crit Care 9: R90–R95, 2005
western Nepal. Nepal Med Coll J 11: 52–56, 2009 30. King TP, Spangfort MD: Structure and biology of stinging insect
10. Mejı́a Vélez G: [Acute renal failure due to multiple stings by Afri- venom allergens. Int Arch Allergy Immunol 123: 99–106,
canized bees. Report on 43 cases]. Nefrologia 30: 531–538, 2010 2000
11. Kidney Disease: Improving Global Outcomes (KDIGO) Acute 31. Terra RM, Guimarães JA, Verli H: Structural and functional be-
Kidney Injury Work Group. KDIGO clinical practice guideline havior of biologically active monomeric melittin. J Mol Graph
for acute kidney injury. Kidney Int 2[Suppl]: 1–138, 2012 Model 25: 767–772, 2007
12. National Kidney Foundation: K/DOQI clinical practice guide- 32. Myatt EA, Stevens FJ, Benjamin C: Solution-phase binding of
lines for chronic kidney disease: Evaluation, classification, and monoclonal antibodies to bee venom phospholipase A2. J Im-
stratification. Am J Kidney Dis 39[Suppl 1]: S1–S266, 2002 munol Methods 177: 35–42, 1994
13. Zhang L, Wang F, Wang L, Wang W, Liu B, Liu J, Chen M, He Q, 33. Yildirim C, Bayraktaroglu Z, Gunay N, Bozkurt S, Köse A, Yilmaz
Liao Y, Yu X, Chen N, Zhang JE, Hu Z, Liu F, Hong D, Ma L, Liu H, M: The use of therapeutic plasmapheresis in the treatment of
Zhou X, Chen J, Pan L, Chen W, Wang W, Li X, Wang H: Preva- poisoned and snake bite victims: An academic emergency de-
lence of chronic kidney disease in China: A cross-sectional sur- partment’s experiences. J Clin Apher 21: 219–223, 2006
vey. Lancet 379: 815–822, 2012 34. Masako M, Hisako H, Eisuke Y, Isao M, Toshiaki A: Koji Mansho,
14. Gauldie J, Hanson JM, Rumjanek FD, Shipolini RA, Vernon CA: Atsumi H. A case of wasp sting disease complicated by multiple
The peptide components of bee venom. Eur J Biochem 61: 369– organopathy: Capability of lifesaving by early diagnosis for
376, 1976 continuous blood filtration and exchange of plasma. Jpn J Clin
15. Han HJ, Lee JH, Park SH, Choi HJ, Yang IS, Mar WC, Kang SK, Lee Exp Med 76: 1355–1358, 1999
HJ: Effect of bee venom and its melittin on apical transporters of 35. Dı́az-Sánchez CL, Lifshitz-Guinzberg A, Ignacio-Ibarra G,
renal proximal tubule cells. Kidney Blood Press Res 23: 393–399, Halabe-Cherem J, Quinones-Galvan A: Survival after massive
2000 (.2000) Africanized honeybee stings. Arch Intern Med 158:
16. Han HJ, Park SH, Lee JH, Yoon BC, Park KM, Mar WC, Lee HJ, 925–927, 1998
Kang SK: Involvement of oxidative stress in bee venom-induced 36. Beccari M Dialysis or plasmapheresis for acute renal failure
inhibition of Na+/glucose cotransporter in renal proximal tubule due to Africanized honeybee stings. Arch Intern Med 159: 1255–
cells. Clin Exp Pharmacol Physiol 29: 564–568, 2002 1256, 1999
17. Liu SI, Cheng HH, Huang CJ, Chang HC, Chen WC, Chen IS, 37. Kellum JA, Levin N, Bouman C, Lameire N: Developing a con-
Hsu SS, Chang HT, Huang JK, Chen JS, Lu YC, Jan CR: Melittin- sensus classification system for acute renal failure. Curr Opin Crit
induced [Ca2+]i increases and subsequent death in canine renal Care 8: 509–514, 2002
tubular cells. Hum Exp Toxicol 27: 417–424, 2008 38. Seabra VF, Balk EM, Liangos O, Sosa MA, Cendoroglo M, Jaber
18. DeGrandi-Hoffman G, Hoffman RF: Bee sting dysphagia. Ann BL: Timing of renal replacement therapy initiation in acute renal
Intern Med 130: 943, 1999 failure: A meta-analysis. Am J Kidney Dis 52: 272–284, 2008
19. Przybilla B, Ruëff F: Insect stings: Clinical features and man- 39. Karvellas CJ, Farhat MR, Sajjad I, Mogensen SS, Leung AA, Wald
agement. Dtsch Arztebl Int 109: 238–248, 2012 R, Bagshaw SM: A comparison of early versus late initiation of
20. Mulfinger L, Yunginger J, Styer W, Guralnick M, Lintner T: Sting renal replacement therapy in critically ill patients with acute
morphology and frequency of sting autotomy among medically kidney injury: A systematic review and meta-analysis. Crit Care
important vespids (Hymenoptera: Vespidae) and the honey bee 15: R72, 2011
(Hymenoptera: Apidae). J Med Entomol 29: 325–328, 1992
21. dos Reis MA, Costa RS, Coimbra TM, Teixeira VP: Acute renal Received: November 28, 2012 Accepted: June 20, 2013
failure in experimental envenomation with Africanized bee
venom. Ren Fail 20: 39–51, 1998 L.Z. and Y.Y. contributed equally to this work.
22. Grisotto LS, Mendes GE, Castro I, Baptista MA, Alves VA, Yu L,
Burdmann EA: Mechanisms of bee venom-induced acute renal Published online ahead of print. Publication date available at www.
failure. Toxicon 48: 44–54, 2006 cjasn.org.

Potrebbero piacerti anche