Selection of sources of evidence
We retrieved 1810 articles ( after removing duplicates) but finally included 28 articles which met the inclusion criteria. The PRISMA flowchart showing the inclusion of studies is presented in Fig. 1.
Characteristics of included studies
The characteristics of included studies are shown in Table 1. (10–33) All studies were single-centre with most of them being cross-sectional in nature. Overall we included a total of 534 renal biopsies and 107 renal autopsy findings. Two studies, (8, 19)were exclusively done on children with a mean age of 11.52 ± 2.88 years and 5.8 ± 1 years respectively. In the majority of studies, AKI was caused by Russell's viper, however, in some studies, Echis carinatus and sea snakes were also identified to be associated with kidney involvement.(9, 12, 18, 27, 34)
Table 1
Characteristics of included studies
|
First Author
|
Year of publication
|
Population
|
Study design
|
State
|
Exclusively done on children
|
Indication/ timing of biopsy
|
Total Number of Snakebite Patients
|
Total Number of snake bite induced AKI cases
|
Total Number of Renal Biopsies
|
Number of patient with persistent renal dysfunction
|
Number of patients who progressed to ESKD
|
Requirement of dialysis
among biopsied patients
|
Died (n)
|
1
|
Chugh et al, (25)
|
1975
|
AKI following snake-bite
|
Cohort with follow-up
|
Chandigarh
|
No
|
NR
|
69
|
8
|
8
|
None
|
None
|
6
|
3
|
2
|
Basu et al, (11)
|
1977
|
Patients with AKI following viperine bite
|
Cross-sectional
|
West Bengal
|
No
|
Early diuretic phase
|
NR
|
45
|
37
|
NR
|
NR
|
31
|
16
|
3
|
Shastry et al, (17)
|
1977
|
Patients with AKI following snake bite
|
Cohort with follow-up
|
Tamilnadu
|
No
|
Day 4 to 31
|
NR
|
19
|
19
|
All patients with ACN
|
NR
|
15
|
1
|
4
|
Sarangi et al, (16)
|
1980
|
AKI following viperine snake bite
|
Cross-sectional
|
Odisha
|
No
|
After oliguric phase of AKI
|
48
|
23
|
22
|
None
|
None
|
1
|
1 patient with ACN
|
5
|
Date et al, (15)
|
1982
|
Patient with AKI following snake bite
|
Cross-sectional
|
Tamil nadu
|
No
|
Biopsy timing varied from 5–22 days.
|
NR
|
9
|
9
|
None
|
None
|
8
|
None
|
6
|
Chugh et al, (10)
|
1984
|
AKI following snake bite. Study was conducted to describe renal histopathological lesions in AKI following snakebite in humans and to know the effects of viperide venoms on the renal structure and function in subhuman primates.
|
Cross-sectional
|
Chandigarh
|
No
|
During the polyuric phase.
|
157
|
45
|
35
|
NR
|
NR
|
NR
|
8 patients with bilateral renal cortical necrosis and 4 patients with ATN died
|
7
|
Date et al, (22)
|
1986
|
Patient with AKI foliowing snake bite
|
Cross-sectional
|
Tamilnadu
|
No
|
NR
|
NR
|
24
|
15
|
All 3 patients of ACN
|
NR
|
22
|
1
|
8
|
Acharya et al,(27)
|
1989
|
AKI following viper-
ine snake bite
|
Prospective
|
Maharashtra
|
4 patients were children below the age of 10years.
|
1.5 to 8 weeks
|
NR
|
50
|
29
|
NR
|
NR
|
45
|
20
|
9
|
Chugh et al, (12)
|
1989
|
All patients with snakebite with treated for viper bite [presumed] poisoning.
|
Cross-sectional
|
Chandigarh
|
No
|
NR
|
246
|
70
|
44
|
NR
|
NR
|
NR
|
NR
|
10
|
BV Mittal et al, (9)
|
1994
|
Patient with AKI following snake bite were included
|
Cross-sectional
|
Maharashtra
|
No
|
Varied from 3–8 weeks
|
253
|
41
|
41
|
NR
|
NR
|
NR
|
6 out of 10 ACN cases died
|
11
|
Chugh et al, (28)
|
1994
|
Patients dialysed for AKI and diagnosed to have ACN
|
Cohort with follow-up
|
Chandigarh
|
No
|
NR
|
16
|
16
|
16
|
NR
|
NR
|
NA
|
NR
|
12
|
Vijeth et al, (27)
|
1997
|
Adult cases of viper bite with systemic envenomation
|
Observational
|
Pondicherry
|
No
|
Persistant renal dysfunction
|
40
|
13
|
3
|
NR
|
NR
|
NR
|
|
13
|
Golay et al, (29)
|
2012
|
Patients with AKI after snake bite
|
Cohort with follow-up
|
West Bengal
|
No
|
In patients who remained oliguric or the serum creatinine did not decrease to less than 50%
of the attained peak value at the end of 3 weeks
|
NR
|
42
|
13
|
5
|
1
|
All 5 AIN patients
|
None
|
14
|
Waikhom et al, (20)
|
2012
|
Post snake bite patients who developed dialysis-requiring AKI
and had survived
|
Prospective observational
|
West bengal
|
No
|
NR
|
499
|
410
|
10
|
10
|
NR
|
10
|
NR
|
15
|
Waikhom et al, (8)
|
2013
|
All pediatric patients with AKI
following Russell’s viper bite
|
Prospective study, supplemented by a retrospective chart
review
|
West bengal
|
Children < 15 years were included
|
NR
|
NR
|
61
|
5
|
NR
|
NR
|
NR
|
NR
|
16
|
Golay et al,
|
2013
|
Post snake bite patients with AKI who had survived
|
Prospective study,
|
West bengal
|
No
|
In whom AKI did not resolve by the end of 3 weeks
|
126
|
-
|
4
|
2
|
NR
|
NR
|
NR
|
17
|
Mukhopadhyay et al, (13)
|
2016
|
All snakebite patient who received hemodialysis
|
Cross-sectional
|
West bengal
|
29 patients were of age ≤ 18 years
|
NR
|
460
|
203
|
3
|
NA
|
NA
|
3
|
NR
|
18
|
Vikrant et al, (23)
|
2017
|
Patients with definitive history of snake bite; clinical picture consistent with snake bite, as
presence of fang marks or cellulitis or coagulopathy or neuroparalysis; presence of AKI as defined using
KDIGO criteria based on serum creatinine and presence of at least one or more indication of RRT
|
Retrospective
|
Himachal pradesh
|
No
|
Patients who remain oligoanuric or whose serum
creatinine did not decrease satisfactorily at the end of 3 weeks underwent kidney biopsy
|
447
|
81
|
22
|
NR
|
NR
|
NR
|
NR
|
19
|
Priyamvada et al, (30)
|
2016
|
Patients diagnosed with snake envenomation-induced AIN
|
Retrospective
|
Puducherry
|
No
|
Renal biopsies are performed if the
serum creatinine remains greater than 2 mg/dL 4 weeks post-envenomation.
|
NR
|
88
|
7
|
One patient had creatinine of 1.6 at 5th month of follow up
|
1 patient remained HD dependant at 3 months of follow up.
|
5
|
None
|
20
|
Dinesh kumar et al, (34)
|
2018
|
Patients with AKI after snake bite and kidney biopsy showing AIN
|
Prospective observational
|
Tamil Nadu
|
No
|
Renal biopsy were performed if kidney dusfunction persisted for more than 3 weeks or earlier if persistant anuria for more than 2–3 weeks or pathology other than ATN was suspected for example fragmented RBCs in peripheral smear.10–40 days
|
196
|
196
|
20
|
During the median follow up of 24 ± 6 months
6 patients developed CKD
|
NR
|
20
|
None
|
21
|
Shaktirajan et al, (24)
|
2018
|
Cases of AKI with renal biopsy showing pigment nephropathy
|
Retrospective observational
|
Tamil Nadu
|
No
|
Patients with persistent oliguria
for > 7 days and renal failure for > 14 days despite supportive
treatment.
|
10
|
10
|
10
|
NR
|
NR
|
NR
|
NR
|
22
|
Priyamvada et al, (18)
|
2020
|
All adult patients with AKI following haemotoxic snake envenomation were recruited
|
Prospective observational
|
Puducherry
|
No
|
Persistant renal dysfunction beyond 3 months
|
420
|
184
|
3
|
During a median follow-up duration of 15.5 months all 3 biopsied patient had persistent renal dysfunction
|
1
|
1
|
None
|
23
|
Rao et al, (33)
|
2019
|
Patients with age > 18 years with definitive history of snake bite(
consistent clinical picture like the presence of
fang marks, cellulitis, coagulopathy,
neuroparalysis) and presence of AKI (as per KDIGO 2012
guidelines)
|
Case-record‐based retrospective
analysis
|
Karnataka
|
No
|
At day 18 in one patient and at day 31 in another patient
|
103
|
103
|
2
|
None
|
1
|
2
|
None
|
24
|
Islam et al (19)
|
2020
|
Paients with hematotoxic snake envenomation characterized mainly by a positive 20 minute whole blood clotting test (WBCT) admitted in pediatric emergency ward
|
Comparative
|
West Bengal
|
Yes ( Mean age 5.8 ± 1) years
|
Children suffering who suffered from permanent renal damage and who died.
|
371
|
139
|
64
|
48
|
NR
|
NR
|
16
|
25
|
Kumar M et al, (14)
|
2022
|
Patients with AKI with 1. Definitive history of snake bite; 2. Clinical picture suggestive of snake bite with the presence of a fang mark.
|
Retrospective recruitment followed by a prospective follow
|
Chennai
|
No
|
NR
|
769
|
159
|
41
|
11
|
1
|
5
|
|
26
|
Ariga et al (26)
|
2021
|
All adult patients with AKI (as per KDIGO criterion) survived the episode and
were discharged
|
Retrospective and prospective observational
(Ambidirectional)
|
Puducherry
|
No
|
NR
|
NR
|
193
|
6
|
3
|
1
|
1
|
0
|
27
|
Acharaya et al, (31)
|
2023
|
All adult patients with AKI (as per KDIGO criterion) following haemotoxic snake envenomation were recruited
|
Prospective
|
Odisha
|
no
|
NR
|
NR
|
202
|
30
|
3
|
3
|
3
|
16
|
28
|
Prema et al, (21)
|
2023
|
Patients with hemoglobulin cast nephropathy
|
Retrospective analysis
|
NR
|
NR
|
NR
|
NR
|
NR
|
16
|
NR
|
NR
|
NR
|
NR
|
NR: Not reported, HD: Hemodialysis, ACN: Acute cortical necrosis
Timing and indication of renal biopsy
In the majority of studies, kidney biopsies were done after 2–3 weeks of the onset of AKI, more so in cases of non-recovery or dialysis dependency. Pathological changes varied depending upon the time lag from the onset of AKI to kidney biopsy. Histopathological findings in Kidney biopsies of included studies are shown in Table 2. Kidney tissue obtained during the early diuretic phase of acute tubular necrosis (ATN) revealed epithelial degeneration in tubules, tubular vacuolation, desquamation, and severe intertubular interstitial oedema with regenerative changes developing at the later stages of AKI (after 3 to 8 weeks). (11, 19, 33) Interstitial haemorrhage was more common in the 1st week of the bite.(27) The nature of the tubular casts also changed with the time lag between the bite and kidney biopsy. Hyaline casts with degenerating cellular-granular casts were more commonly observed in earlier stages whereas red blood cells (RBC) casts appeared later.
Table 2
Kidney biopsy findings chart
SL No
|
Primary Author
|
Light microscopy
|
IF
|
EM
|
Glomerular changes
|
Tubulointerstitial changes
|
Vascular changes
|
1
|
Chugh et al 1975, (25)
|
ACN in 50% of the cases. Surviving glomeruli in areas of necrosis showed fibrin thrombi and some proliferation of mesangial cell
|
ATN in 50% of the cases
|
Not mentioned specifically
|
NR
|
NR
|
2
|
Basu et al, 1977, (11)
|
ACN in 2 (5.4%) of the cases. Glomerular tuft necrosis (13.4%),Isolated Glomerular thrombosis (19%)
|
ATN in 32 (86.4%) cases. Peritubular infiltration of inflammatory cells (16.2%)
Medullary haemorrhage (27%)
|
Vessel wall necrosis (13.4%)
Fibrin thrombi in arteriole (5.4%)
|
NR
|
NR
|
3
|
Shastry et al, 1977 (17)
|
ACN in 3 (15.7%) of the cases. Focal mesangial hypercellularity in 32%.
|
ATN in 12 (63.2%) of cases, Interstitial haemorrhage (15.7%). Presence of hyaline, granular and heme cast. Vacuolation and regeneration. Intertitial fibrosis in 1 case
Interstitial oedema (10.5%)
Interstitial inflammation (52.6%)
|
Not mentioned specifically
|
NR
|
NR
|
4
|
Sarangi et al, 1980, (16)
|
ACN in one case. Aneurysmal capillary dilatation and inflammatory cell infiltration were seen in glomerulus
|
Acute tubular injury (n = 3), Acute tubular necrosis (n = 6), Presence of interstitial haemorrhage oedema (5 cases) and RBC tubular cast.
|
Not mentioned specifically
|
NR
|
NR
|
5
|
Date et al, 1982, (15)
|
Glomeruli was normal except for focal mesangial expansion and focal prominence of parietal epithelium. One case had necrosis of cortical tissue
|
ATN (n = 9) .The interstitium was expanded and infiltrated by mononuclear cells and scattered eosinophils predominantly at the cortico-medullary junction.
|
No abnormality
|
NR
|
Glomeruli: Swollen bowman’s capsule epithelium containing numerous organelles. The visceral epithelium revealed microvilli, patchy foot process fusion and intracytoplasmic lipid vacuoles..
Glomerular capillaries had irregular thickening and wrinkling of glomerular basement membrane.
Mesangial expansion was present in all biospies.
Subendothelial electron dense deposits were seen in one case and one case had features of ACN.
Blood vessels: Swollen endothelial cells containing numerous vacuoles and a dilated smooth endoplasmic reticulum.
Interstitium: Oedematus intertubular tissue and infiltration of inflammatory cells including eosinophils, 6mast cells, plasma cells and lymphocytes and some macrophages and basophils.
|
6
|
Chugh et al, 1984, (10)
|
ACN (n = 10). Superficial cortical glomeruli were more severely congested compared to deep juxtamedullary glomeruli. Hilar glomerular capillaries were partly filled with recent thrombus.
|
ATN (n = 23). PCT showed shrunken, pyknotic nuclei or no stainable nuclei with cytoplasmic cloudy swelling and considerable tubulorrhexis. Distal convolutions were collapsed. Collecting ducts contained brown heme casts or pigments.
|
The large intrarenal arteries were deeply congested. The intertubular capillaries were crowded with neutrophils. In some cases venules and veins were congested with inflammatory cells.
|
NR
|
NR
|
7
|
Date et al, 1986
|
ACN (n = 3)
|
ATN ( n = 12)
|
NR
|
Not done
|
Done in 7/15 biopsies. Biopsies revealed platelet and fibrin clusters in glomeruli and small calibre vessels
|
8
|
Acharya et al, 1989
|
ACN in 7 cases. Ballooning of glomerular capillaries (n = 10), swollen endothelial cells (n = 10), splitting of basement membrane (n = 19).
Mesangial cell proliferation (n = 5). Proliferative glomerular changes in 5 cases.
|
ATN in 10 cases with evidence of tubular degeneration in 17.% cases
|
Vasculitis like changes in vessels.7% cases. Fibrin thrombi in capillaries 24.2% cases.
|
Not done
|
Not done
|
9
|
Chugh et al, 1989
|
Patchy ACN in 4 cases and diffuse cortical necrosis in 8 patients.
|
ATN was present in 32 (73%) of cases, AIN in 3 patients.
|
Necrotizing arteritis of the interlobular arteries along with thrombophlebitis of the arcuate vein and its tributaries in 2 cases.
|
Dense deposits of C3 were seen in the walls of afferent and efferent arterioles in cases of necrotizing arteritis.
|
Not done
|
10
|
Mittal et al, 1994
|
ACN in 25 (60.9%) cases. Focal proliferation of mesangial cell (12.1%). Mild mesangial proliferation (53.6%).
Mesangiolysis (17.7%)
Ballooning of glomerular capillaries (31.7%), swollen endothelial cells (39%), splitting of basement membrane (26.8%). Capillary thrombi (12.1%).
|
Tubular necrosis (12.1%), Tubular regeneration (4.8%). Pyelonephritis complicating tubular necrosis and one autopsied case revealed abscesses. Haemorrhagic interstitial nephritis with haemorrhage in subcapsular area in case.
|
Other than in cases of ACN. Not mentioned specifically
|
Done in 7 cases
IgG (weak +):2 cases
IgM (weak +):1
case
C3 (+):2 cases in mesangial area.
Presence of fibrin in mesangial area: 1 case
|
Not done
|
11
|
Chugh et al, 1994
|
ACN in all 16 patients
|
NR
|
NR
|
NR
|
NR
|
12
|
Vijeth et al.
|
NR
|
ATN in 3 (100%) cases
|
NR
|
NR
|
NR
|
13
|
Golay et al, 2012
|
Normal glomeruli
|
ATN in 8 (21.5% ) and AIN in 5 (11.9%) cases.
Extensive interstitial inflammation was observed in all the AIN cases, with pre-dominantly lymphocytic infiltration, in one case where eosinophils were predominant.
|
Normal Blood vessels
|
No IF deposits
|
NR
|
14
|
Waikhom et al, 2012
|
ACN in 3 patient
|
ATN in 6 patients. AIN in1 case
|
Not specifically mentioned
|
NR
|
NR
|
15
|
Waikhom et al, 2013,
|
ACN in one case.
|
ATN in 3 patients. AIN in1 case
|
Not specifically mentioned
|
NR
|
NR
|
16
|
Golay et al, 2013
|
ACN in one case
|
ATN in 3 patients
|
Not specifically mentioned
|
NR
|
NR
|
17
|
Mukhopadhyay et al, 2016
|
ACN in one patient
|
ATN in 2 patients
|
NR
|
NR
|
NR
|
18
|
Vikrant et al, 2017
|
Patchy ACN in one case.
|
ATN in 20 (91) cases. In 9 (40.9%) ATN was associated with mild to moderate AIN. One (4.5%) patient only had moderate AIN
|
Not specifically mentioned
|
Findings not specifically mentioned
|
NR
|
19
|
Priyamvada et al, 2016
|
Diffuse mesangial
proliferation;
in 1out of 5 case. Rest were normal
|
ATN in 4 cases. AIN in 5 out of 7 cases.
Lymphocyte-predominant infiltration in all patients. 4 patients had admixture of other cell types including eosinophils, neutrophils, and plasma cells.
Neutrophil cast in was seen 1 patient.
|
Not specifically mentioned
|
Weak 1 + C1q deposits in mesangium of 1 patient
|
NR
|
20
|
Dinesh kumar et al, 2018
|
Not specifically mentioned
|
AIN was reported in 20 ( 23.5%) out of 85 biopsies.
Marked infiltration of eosinophils and lymphocytes was seen along with tubular injury.
|
Not specifically mentioned
|
Negative in all patients
|
NR
|
21
|
Shaktirajan et al, 2018
|
None of the patients had significant glomerulosclerosis or any other specific glomerular abnormality
|
Snake bite envenomation was present in 10 out of 46 patient of pigment induced nephropathy.
All renal biopsies revealed acute tubular injury with pigment casts in the tubules. No interstitial fibrosis or tubular atrophy were noted
|
Not specifically mentioned
|
NR
|
NR
|
22
|
Priyamvada et al 2020
|
1 out of 2 patients had features of chronic TMA
|
Not specifically mentioned
|
Not specifically mentioned
|
NR
|
NR
|
23
|
Rao et al, 2019
|
Biospsy of both patient was suggestive of ACN with fibrin thrombi in glomerular capillary lumen and arterioles. TMA was present in both cases.
|
One biopsy showed evidence of AIN along with TMA
|
Fibrin thrombi was present in in glomerular capillary lumen and arterioles.
|
NR
|
NR
|
24
|
Islam et al, 2020,(19)
|
ACN in 12.5% cases.
|
ATN in 39.1%. cases
|
NR
|
NR
|
NR
|
25
|
Kumar M et al, 2022
|
• 5 out of 41 had ACN.
• 4 out of 41 had TMA
• One patient had TMA with renal cortical necrosis
|
• ATN in 44% cases.
• 5 biopsies showed pigmented casts
• AIN was reported in 9
( 22%).
• 5 cases had ATN with AIN
|
NR
|
NR
|
NR
|
26
|
Ariga et al, 2021
|
NR
|
Out of 6, 2 were ATN and 4 were AIN
|
NR
|
NR
|
NR
|
27
|
Acharya et al, 2023
|
• ACN in 23%
|
• AIN was reported in 9
( 22%).
• ATN in 44% cases.
|
NR
|
NR
|
NR
|
28
|
Prema et al
|
NR
|
• 16 patients with ATN alongside hemoglobulin cast nephropathy.
• Hemoglobin casts were seen present in the PCT. The casts were bright red to brown on hematoxylin and eosin stain weakly PAS positive, argyrophilic on Jones methenamine silver stain, and granular to globular in texture. Hemoglobin IHC was positive on the pigment casts. Two patients showed myoglobin immunostain positivity.
|
NR
|
NR
|
NR
|
NR: Not reported, HD: Hemodialysis, ACN: Acute cortical necrosis, ATN : Acute tubular necrosis, AIN: Acute interstitial nephritis, TMA: Thrombotic microangiopathy, PCT: Proximal convoluted tubules, PAS: periodic acid-Schiff, IHC: immunohistochemistry |
Renal Biopsy findings
Glomerular lesions
Changes in the glomerulus were largely underreported. Glomerular changes occurring with acute cortical necrosis (ACN) were the most commonly reported finding. (8–10, 12–17, 19, 20, 27, 28, 31) However, thrombotic microangiopathy (TMA) and focal and diffuse mesangial proliferation have also been reported. (14, 33) Studies also reported necrosis of glomerular tuft and isolated glomerular thrombosis. (11) Specific glomerular changes like ballooning and dilatation in the glomerular capillary loops, focal proliferation of mesangial cells, endothelial cell swelling, splitting of glomerular capillary basement membrane were reported by Mittal et al and Acharya et al. (9, 27)
Tubulointerstitial Changes
ATN was the most frequently encountered finding in kidney biopsy tissue. The incidence varied from 30–100%. (8, 9, 11, 12, 14–16, 18, 23, 25–27, 32, 34) Hyaline, granular, or pigment casts were frequently seen along with dilated tubules lined with flattened epithelium and desquamation of necrotic cells. (12, 28) Acute interstitial nephritis (AIN) has been reported non uniformly. (14, 23, 30, 31, 34) In a series by Priyamvada et al, 5.7% of snakebite-induced AKI were reported to have AIN on kidney biopsy. (30) The kidney biopsy demonstrated mixed infiltrate of predominantly lymphocytes and variable proportions of other cells like neutrophils, eosinophils, and occasional plasma cells. Neutrophil cast was reported in one patient. The incidence of AIN was slightly higher in other series; out of 85 biopsies, 20 (23.5%) patients had AIN. (34) Marked infiltration of eosinophils and lymphocytes with substantial tubular injury was reported. Golay et al. observed extensive interstitial inflammation, with a predominant lymphocytic infiltration. (20) In viperine poisoning, “hemorrhagic interstitial nephritis” characterized by haemorrhages in the interstitium with tubular necrosis and RBC congestion in the tubular lumen was reported. (9, 17) One study reported features of pyelonephritis complicating ATN. (9) Patchy and diffuse areas of hemorrhagic necrosis in the cortex and widespread medullary areas have also been reported in in Russell viper’s envenomation. (11)This peculiar finding is usually not associated with AKI due to other etiologies.
-
Pigment induced nephropathy
Sakthirajan et al, in their analysis of pigment-induced nephropathy, found snake envenomation as the most frequent etiology of rhabdomyolysis. (24) Out of the 26 patients with rhabdomyolysis, 10 were caused by snakebite envenomation. All biopsies revealed features of acute tubular injury and pigment casts. I an another series, among a cohort of 56 patients diagnosed with hemoglobin cast nephropathy, the second most prevalent etiology, following drug-induced cases, was attributed to snake envenomation-induced hemolysis. This particular cause was observed in 16 patients, accounting for approximately 28.4% of all patients. Positive myoglobin immunostaining was observed in two patients who had suffered snake bites envenomation. (21)
Vascular changes
Vasculitis-like changes including necrotizing arteritis, thrombophlebitis, and vessel wall necrosis have been described in Russell's viper bite cases. (10, 11, 27) Severe congestion of large intrarenal vessels along with venules and veins and crowding of neutrophils in intertubular capillaries were reported by Chugh et al. (12)
Thrombotic microangiopathy
TMA has been rarely reported in snake-bite AKI. Rao et al described a series of TMA in AKI induced by snake-bite envenomation. (33) In this study, out of 103 patients post snake-bite envenomation AKI, 19 (18.5%) had clinical features of TMA. Priyamvada et al also reported chronic TMA in patients who developed CKD following snakebite envenomation. (18)
Acute cortical necrosis (ACN)
Following ATN, ACN was the second most common finding reported in patients with snake-bite AKI. Its incidence varies between 5–100% of biopsies reporting it. (8–10, 12–17, 19, 20, 27, 28, 31) Fibrin and platelet thrombi were found predominantly in lobar and sublobar arteries. In an analysis by Chugh et al including 113 cases of ACN, viperine snake-bite envenomation was one of the major causes responsible for 16 (14.2% ) of total ACN cases. (28)
Immunofluorescence (IF)
Only a few studies reported IF findings. (9, 25, 29, 30, 34) A study showed dense C3 deposits in the afferent and efferent arteriolar walls in cases of necrotizing arteritis. (12) Mittal et al demonstrated IF results in 7 patients and reported a weak positivity for IgG and IgM, along with C3 positivity in the mesangial area. Priyamvada et al found a weak C1q deposition in the mesangium. (30) Other studies failed to demonstrate any deposits in IF. (29, 34)
Electron microscopy
Studies describing electron microscopic findings were scanty. (15, 22) Date et al provided a detailed description of ultrastructural findings. The authors reported swollen cytoplasm of bowman’s capsule epithelium with visceral epithelium showing blebs, microvilli, patchy foot process fusion, and intracytoplasmic lipid vacuoles. The basement membrane of the glomerular capillaries was thick and wrinkled. In blood vessels, endothelial cells were swollen and cytoplasmic protrusions were seen to be protruding into the lumen. Infiltration of inflammatory cells was found in the interstitium. Intracytoplasmic bodies were seen in the proximal tubules representing degenerating organelles.
Renal biopsy findings and outcomes
The kidney outcomes in AKI following snakebite envenomation varied from partial or complete recovery of kidney functions to progression to end-stage kidney disease (ESKD) resulting in dialysis dependence. Studies reported that snakebite envenoming patients who did not recover their kidney functions had diffuse cortical necrosis and thrombotic microangiopathy as the predominant pathological findings. Patients with acute tubular injury were reported to respond well to conservative management and dialysis contrary to those with ACN who only responded partially or not at all. (17) Sarangi et al demonstrated that the clinical presentation and prognosis of the patients were directly proportional to the severity of renal histopathological lesion on the kidney biopsy. (16) Lower survival rates were reported in ACN. 8 out of 10 patients (80%) who had bilateral renal cortical necrosis, and 4 out of 23 patients with less severe acute tubular lesions died (P < .001). Other series reported a mortality rate of up to 100% in patients with ACN. (25)
Studies also reported that as compared to non-TMA cases of AKI, TMA cases were associated with more advanced azotemia at presentation with an almost universal requirement for dialysis. These patients required a longer duration of renal replacement therapy (RRT), and hospitalization and had higher chances of progressing into chronic kidney disease (CKD) with higher mortality insinuating a poor prognosis. (18, 33) Golay et al reported worse clinical outcomes while comparing cases with and without AIN. (29)
Use of steroids
There were three studies on the use of steroids. (29, 30, 34) Studies reported a steroid recovery rate of 20, 80%, and 70% respectively. The dose of steroid used in Dinesh et al (34) study was 0.5mg/kg/day for two weeks tapered over a month. Despite treatment with steroids, 30% of patients progressed to CKD. Based on these findings it is difficult to ascertain whether the application of early biopsy and prompt treatment of AIN with steroids would prevent the progression to CKD. The time period lapsed from the inciting event at which steroids can elicit a favorable response in AIN is also yet to be determined.