Neutrophil Gelatinase–Associated Lipocalin Acts as a Robust Early Diagnostic Marker for Renal Replacement Therapy in Patients with Russell’s Viper Bite–Induced Acute Kidney Injuries

Abstract

Snakebite-induced acute kidney injury (AKI) is frequently observed in patients following bites from vipers such as Russell’s viper (Daboia russelii) in India. Currently, the levels of serum creatinine are mainly used as a marker to determine the necessity for renal replacement therapy (RRT) (haemodialysis) in severe cases of AKI. However, it takes up to 48 h to ascertain a distinct change in creatinine levels compared to its baseline level upon admission. The time lost between admission and the 48 h timepoint significantly affects the clinical management of snakebite victims. Moreover, early diagnosis of AKI and decision on the necessity for RRT in snakebite victims is critical in saving lives, reducing long-term complications, and minimising treatment costs arising from expensive haemodialysis. Neutrophil gelatinase–associated lipocalin (NGAL) has been recently studied as a robust early marker for AKI in non-snakebite patients. However, its suitability for clinical use in snakebite victims has not been rigorously established. Here, we demonstrate the clinical significance of plasma NGAL as a robust marker for RRT following AKI using a large cohort (309) of Russell’s viper victims without any pre-existing health conditions. NGAL levels upon admission are positively correlated with creatinine levels at 48 h in different stages of AKI. Overall, NGAL acts as a robust early marker to ascertain the need for RRT following Russell’s viper bites. The quantification of NGAL can be recommended as a routine test in hospitals that treat snakebites to decide on RRT at early time points instead of waiting for 48 h to confirm the increase in creatinine levels. The diagnostic use of NGAL in Russell’s viper victims with pre-existing comorbidities and for other vipers should be evaluated in future studies.

Urinary proteomics reveals biological processes related to acute kidney injury in Bothrops atrox envenomings

“…In addition to the mentioned markers, other appointed indicators of kidney injury, such as kininogen-1 (KNG1), aminopeptidase-N (ANPEP), and glutathione S-transferase P (GTSP) [42][43][44][45][46][47][48][49], were found in our data (S1 File, tab S1); however, they did not present a significant abundance or difference among the studied groups.…”

“…Their abundance in the urine of No-AKI patients may suggest a protective role in Bothrops snakebite envenoming. Lastly, NGAL, AHSG, and clusterin displayed no significant differential abundance in Bothrops snakebite-induced AKI, despite being described as promising biomarkers candidates for AKI development, even in viper envenoming [ 18 , 42 , 43 , 45 ]. Others, such as angiopoietin-1 (ANG1), kidney injury molecule-1 (KIM-1), and the urinary monocyte chemotactic protein-1 (MCP1) were not identified [ 22 ].…”

Peripheral Arterial Thrombosis following Russell's Viper Bites

“…Bleeding complications (hemorrhage) from SBE inflicted by many viperid species are commonly reported and they can lead to cerebral hemorrhage, 28 29 pituitary failure, 30 pseudoaneurysm, 15 perinephric hematoma, 31 32 and acute kidney injury. 33 These complications can also contribute to the onset of cardiovascular shock and multiple organ failure. However, thrombosis, specifically peripheral arterial thrombosis, is a rare (but serious) phenomenon following SBE.…”

Development of Wunderlich syndrome following a Russell’s viper bite

“…The bites from Russell's viper are known to induce local inflammation, tissue damage, coagulopathies often resulting in haemorrhage, neurotoxicity and nephrotoxicity [7][8][9]. Notably, the development of acute kidney injury (AKI) following Russell's viper bites is common and it often necessitates expensive renal replacement therapy [10,11]. Russell's viper bites are also known to induce several rare envenomation effects such as priapism [12], splenic rupture due to excessive haemorrhage [13] and sialolithiasis (development of calculi in salivary glands) [14] among others.…”