Increase, Renal pathology due to VTG deposition leads to Increased Mortality

The kidneys perform a suite of physiological roles that are critical for organismal homeostasis including waste excretion, osmoregulation, and fluid homeostasis (Preuss, 1993). The renal system can incur damage from a variety of sources which can lead to a loss of renal functions such as decreased glomerular filtration rate or impaired clearance of waste products which can lead to death (McKee & Wingert, 2015).

For example, in fish exposed to estrogenic compounds there is evidence that excessive production of vitellogenin (VTG), which leads to renal failure, increases mortality in fish (Herman & Kincaid, 1988). Generally, the molecular mass of proteins in glomerular filtrate are lower than albumin but when proteins like VTG are deposited in the kidneys they cannot be resorbed and the excess protein can lead to glomerular rupturing or hemorrhaging (Tojo & Kinugasa, 2012). Ultimately these pathologies can cause acute renal failure resulting in mortality.

• Male summer flounder injected with 17β-estradiol (E2) had increased levels of circulating VTG. The accumulation of VTG resulted in obstruction or rupture of renal glomeruli. Glomerular injury including immunoreactive hyalin material within the glomerular capsule, increased drainage into Bowman’s space and renal tubules. Mortality observed after E2 treatment likely resulted from  acute renal failure associated with excessive VTG accumulation in the kidney (Folmar et al., 2001).
• High mortality was observed in rainbow trout fed E2. The accumulation of circulating VTG most likely resulted in hypertrophy of the kidneys (Herman & Kincaid, 1988). 
• Abdel-Tawwab et al. (2020) found that in European sea bass fed dietary zearalenone combined with exposure to a pathogen, Vibrio alginolyticus, increased mortality. A depletion of serum total protein, albumin, and globulin was observed in in zearalenone fed fish which resulted in kidney dysfunction and ultimately increased mortality.
• Exposure to microcystin-LR (MC-LR) resulted in kidney lesions consisting of coagulative tubular necrosis with a dilation of Bowman's space and caused mortality in rainbow trout (Kotak et al., 1996). Mortality is most likely due to MC-LR resulting in significantly dysregulating proteins related to ionic regulation (Shahmohamadloo et al., 2022).
• Laboratory in vivo aquatic exposures of fathead minnow to EE2 led to renal pathology within 16 weeks, concomitant with macroscopic evidence of osmoregulatory dysfunction and morbidity (Länge et al., 2001). 
• Proliferative kidney disease caused by Tetracapsuloides bryosalmonae in salmonid fish result in significant kidney lesions and often resulted in mortality (e.g., Bettge et al., 2009; Schmidt-Posthaus et al., 2015; Sterud et al., 2007).
• In male fathead minnows exposed to the estrogenic PFAS FC-10 diol for 21 days neuropathy in the kidneys was observed, specifically tubule dilation, tubule protein, enlarged glomeruli, glomerular protein, and thickened basement membranes. Additionally, interstitial and intravascular proteinaceous fluid was significantly elevated. Elevated mortality in males was also observed (Ankley et al. in prep).