Clinicopathological spectrum of snake bite-induced acute kidney injury from India

Table 1 Demographic and clinical characteristics of the study patients (n = 121)

Gender
Male, n (%)	51 (42.1)
Female, n (%)	70 (57.9)
Age (yr)
Mean ± SD	42.2 ± 15.1
Range	14-84
Month of the bite
March, n (%)	1 (0.8)
April, n (%)	8 (6.6)
May, n (%)	10 (8.3)
June, n (%)	20 (16.5)
July, n (%)	16 (13.2)
August, n (%)	22 (18.2))
September, n (%)	29 (24)
October, n (%)	10 (8.3)
November, n (%)	5 (4.1)
Duration at arrival (d)
Mean ± SD	3.4 ± 3.7a
Median	3
Range	1-30
Duration of hospital stay (d)
Mean ± SD	12.4 ± 7.7a
Median	10
Range	1-40
Bite site
Lower limb, n (%)	75 (85.2)
Upper limb, n (%)	13 (14.8)
Oliguria, n (%)	70 (79.5)a
Hematuria, n (%)	48 (54.5)a
Limb swelling/cellulitis, n (%)	12 (13.6)a
Neurotoxicity, n (%)	5 (5.7)a
Coagulation defect, n (%)	78 (88.6)a
ASV given, n (%)	85 (96.6)a
Blood transfusion, n (%)	15 (17)a
ICU support, n (%)	10 (11.4)a
Dialysis therapy, n (%)	99 (81.8)
Hemodialysis
Mean ± SD	3.5 ± 3.7
Median	3
Range	1-20
Outcome
Survived, n (%)	110 (90.9)
Died, n (%)	11 (9.1)

^aClinical details avaiable in 88 patients. ASV: Anti-snake venom; ICU: Intensive care unit.

Table 2 Laboratory results of the study patients (n = 88)

	Mean ± SD	Range
Hemglobin (g/dL)	9.6 ± 2.6	3.8-16
WBC count (× 103/mm3)	15 ± 7.4	4.8-47.9
Platelets (× 103/mm3)	117 ± 58	18-230
Urea (mg/dL)	169 ± 75	54-440
Creatinine (mg/dL)	7.2 ± 4.2	1.6-19.2
Sodium (mEq/L)	134 ± 8.1	108-145
Potassium (mEq/L)	5 ± 0.8	3.2-7.2
Albumin (g/dL)	3.2 ± 0.4	2.5-4.1
Bilirubin (mg/dL)	1.4 ± 1.4	0.3-7.5
AST (U/L)	152 ± 296	16-1606
ALT (U/L)	106 ± 163	10-800
Alk. phosph. (U/L)	93 ± 66	18-432
CK (U/L)	2072 ± 4287	24-22000
LDH (U/L)	1153 ± 1015	70-4705

ALP: Alkaline phosphatase; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; CK: Creatine kinase; LDH: Lactate dehydrogenase; Alk. phosph.: Alkaline phosphatase.

Table 3 Frequency of various of hematological and biochemical disorders (n = 88)

Anemia Hb < 12 g/dL, n (%)	71 (80.7)
Leukocytosis, n (%)	66 (75)
Thrombocytopenia, n (%)	42 (47.7)
Hyperkalemia, n (%)	22 (25)
Severe metabolic acidosis, n (%)	35 (39.8)
Hepatic dysfunction, n (%)	36 (40.9)
Hypoalbuminemia, n (%)	54 (61.4)
Hemolysis, n (%)	75 (85.2)
Rhabdomyolysis, n (%)	60 (68.2)

Table 4 Complications in the study patients (n = 88)

Pneumonia/ARDS	8 (9.1)
Hypertension	8 (9.1)
Hypotension	4 (4.5)
Myocarditis	1 (1.1)
Myocardial infarction	1 (1.1)
Gastrointestinal bleed	11 (12.5)
DIC	8 (9.1)
Seizure/Encephalopathy	9 (10.2)
MOF	4 (4.5)

DIC: Disseminated intravascular coagulation; MOF: Multi organ failure; ARDS: Acute respiratory distress syndrome.

Table 5 Comparison of demographic and laboratory results between survival and non survival group (n = 88)

	Survived (n = 79)	Died (n = 9)	P value
Age (yr)	43 ± 15.7	39 ± 12.2	0.460a
Sex
Male, n (%)	34 (43)	2 (22.2)	0.299c
Female, n (%)	45 (57)	7 (77.8)
Duration at arrival (d)	3.4 ± 3.9	2.9 ± 0.8	0.536b
Duration of hospital stay (d)	12.9 ± 7.2	8.8 ± 11.4	0.012b
Hemoglobin (g/dL)	9.6 ± 2.7	8.9 ± 2.4	0.435a
WBC count (× 103/mm3)	14.5 ± 7.3	19.7 ± 7.5	0.023b
Platelets (× 103/mm3)	119 ± 57	95 ± 67	0.218
Urea (mg/dL)	167 ± 78	186 ± 43	0.466
Creatinine (mg/dL)	7 ± 4.1	7 ± 2	0.997
Sodium (mEq/L)	135 ± 8	138 ± 4.6	0.182
Potassium (mEq/L)	4.8 ± 0.8	5.1 ± 1.2	0.392
Albumin (g/dL)	3.3 ± 0.4	3 ± 0.3	0.005
Bilirubin (mg/dL)	1.2 ± 1.1	3.1 ± 2.2	0.006b
AST (U/L)	141 ± 283	254 ± 398	0.231b
ALT (U/L)	101 ± 158	156 ± 200	0.102b
ALP (U/L)	90 ± 67	122 ± 54	0.057b
CK (U/L)	1811 ± 3762	4069 ± 7181	0.298b
LDH (U/L)	1106 ± 1027	1684 ± 732	0.052b

^aIndependent samples t-test, sig. (2-tailed);

^bMann-Whitney U test, Sig. (2-tailed), non parametric independent samples test;

^cχ² with Fisher’s Extact test Exact sig. (2-sided). ALP: Alkaline phosphatase; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; CK: Creatine kinase; LDH: Lactate dehydrogenase.

Table 6 Comparison of clinical characteristic, laboratory abnormalities and complications between survival and non survival group (n = 88)

	Survived (n = 79)	Died (n = 9)	P valuea
Oliguria, n (%)	62 (78.5)	8 (88.9)	0.679
Hematuria, n (%)	44 (55.7)	4 (44.4)	0.726
Anemia, n (%)	64 (81)	7 (77.8)	1.000
Leukocytosis, n (%)	57 (72.2)	9 (100)	0.105
Thrombocytopenia, n (%)	37 (46.8)	5 (55.6)	0.731
Hyperkalemia, n (%)	19 (24.1)	3 (33.3)	0.685
Metabolic acidosis, n (%)	29 (36.7)	6 (66.7)	0.147
Hypoalbuminemia, n (%)	46 (58.2)	8 (88.9)	0.145
Hepatic dysfunction, n (%)	32 (40.5)	4 (44.4)	1.000
Hemolysis, n (%)	67 (84.8)	8 (88.9)	1.000
Rhabdomyolysis, n (%)	55 (69.6)	5 (55.6)	0.457
Pneumonia/ARDS, n (%)	3 (3.8)	5 (55.6)	0.001
Seizure/Encephalopathy, n (%)	5 (6.3)	4 (44.1)	0.005
Multiorgan failure, n (%)	2 (2.5)	2 (22.2)	0.050
ICU support, n (%)	5 (6.3)	5 (55.6)	0.001
Dialysis, n (%)	57 (72.2)	9 (100)	0.105

^aχ² with Fisher’s Extact test. ICU: Intensive care unit; ARDS: Acute respiratory distress syndrome.

Table 7 Kidney biopsy results (n = 22)

Acute tubular necrosis, n (%)	11 (50)
Acute tubular necrosis + acute interstitial nephritis, n (%)	9 (40.9)
Acute interstitial nephritis, n (%)	1 (4.5)
Acute cortical necrosis, n (%)	1 (4.5)

Table 8 Studies of snake bite-induced acute kidney injury

Ref.	Chugh[9]	Pinho et al[11]	Athappan et al[20]	Danis et al[21]	David et al[22]	Dharod et al[23]	Harshavardhan et al[24]	Albuqerque et al[25]	Krishnamurthy et al[26]	Li et al[27]	Naqvi et al[28]	Singh et al[29]	Mukhopadhyay et al[30]	The present study
Year	1989	2005	2008	2008	2012	2013	2013	2014	2015	2016	2016	2016	2016	2016
Place	Chandigarh	São Paulo	Madurai	Diyarbakir	Vellore	Nagpur	Hassan	Fortaleza	Puducherry	Chengdu	Karachi	Barabanki	Kolkata	Shimla
Country	India	Brazil	India	Turkey	India	India	India	Brazil	India	China	Pakistan	India	India	India
Type of study	Retrospective	Prospective	Prospective	Retrospective	Retrospective	Prospective	Prospective	Retrospective	Prospective	Retrospective	Retrospective	Retrospective	Prospective	Retrospective
Time period (yr)	22	3.6	2	7	10	1.7	1	10	1.6	1.8	25	1.5	1.3	13
Total patients (n)	246	100	1548	200	533	281	246	276	61	119	-	138	460	-
AKI, n (%)	70 (28)	29 (29)	159 (10.3)	16 (8)	143 (26.8)	87 (31)	36 (14.6)	42 (15.2)	28 (45.9)	16 (13.4)	115	62 (44.9)	155 (33.7)	121 (18.1)b
Age (yr) mean ± SD	27.1 ± 15.8	24	39.1	40.3 ± 18.8	32 ± 15.9	36.1 ± 14.6	41.2 ± 12.4	43 ± 20	8	66 ± 7	35.9 ± 15	34.1 ± 1.6	36.3 ± 1.3	42.2 ± 15.1
Male (%)	-	83	56.7	50	69.4	70.1	55.5	76.2	53.6	50	62	80.6	69	42.1
Duration at arrival (d) Mean ± SD	-	< 0.5	0.9	0.1 ± 0.1	< 1	0.9 ± 1.8	0.9	1	0.2	1.3 ± 0.9	8.8 ± 5.6	2.8 ± 1.3	3.2a	3.4 ± 3.7
Bite site at lower limb (%)	-	83	98.7	88	71.7	78.2	81.2	-	-	-	-	-	88.7	85.2
Oligo-anuria, n (%)	94	13.8	100	37.5	-	100	94	-	60.7	-	94	-	66	79.5
Hematuria (%)	80	83	70	-	64.3	-	80	-	24.6	-	-	58.1	-	54.5
Limb swelling/cellulitis (%)	-	98.7	-	-	92	91.6	0	57.1	39	-	41	51.6	63.2	13.6
Hypotension (%)	16	-	17.7	-	-	19.5	33.3	-	-	6.3	-	45.2	33.5	4.5
Neurotoxicity (%)	-	100	-	-	-	12.1	-	28.6	-	-	12.1	3.2	-	5.7
Bleeding/coagulopathy (%)	-	83	27.8	-	-	83	38.8	52.4	37.7	-	65.2	50	65.8	88.6
Hemoglobin (g/dL)	7 ± 2.6	-	-	13.2 ± 3.4	-	7.2 ± 1.4	-	9.4 ± 2.5	-	13.3 ± 1.2	8.3	-	-	9.6 ± 2.6
WBC count (× 103/mL)	-	-	-	19.3 ± 3.7	-	-	-	13.6 ± 5.2	-	11.5 ± 3.8	13.2	-	-	15 ± 7.4
Urea (mg/dL)	233 ± 107	-	100	113 ± 78	-	163 ± 83	85 ± 29.2	107 ± 74	-	-	-	-	-	169 ± 75
Creatinine (mg/dL)	9.2 ± 3.4	-	4.2	2.9 ± 0.5	-	4.9 ± 2.5	3.1 ± 1.5	3 ± 2.9	-	-	-	-	4.6 ± 0.2	7.2 ± 4.2
Hemolysis (%)	54	-	28.1	-	-	-	13.8	-	-	-	-	-	-	85.2
Thrombocytopenia (%)	14	-	25.2	60	-	-	-	-	-	-	-	-	9.7	47.7
DIC (%)	43	-	27.8	25	-	-	11.1	-	-	-	-	-	27.1	9.1
RRT (%)	75.7	24.1	45.3	25	57	55.2	44.4	30.6	35.7	-	92.2	-	100	81.8
DOHS (d)	-	-	5	6.7 ± 3.6	-	-	9	8	8	11.6 ± 2.7	-	-	11	10
Mortality (%)	28.6	10.3	22.6	18	21	39.1	22.2	0	14.3	6.3	13	-	29.7	9.1

^aBite to hemodialysis initiation time;

^bEighty-one (18.1%) out of total of 447 snake bite had AKI. DIC: Disseminated intravascular coagulation; RRT: Renal replacement therapy; DOHS: Duration of hospital stay.