ABSTRACT
The protective effect of estrogens against chronic glomerular diseases is admitted but remains debated during acute kidney injury (AKI). Using a model of resuscitated hemorrhagic shock in C57/Bl6 female mice, this study evaluated at 1 and 21 days the renal effect of (1) endogenous estrogen, using ovariectomized mice with or without chronic estrogen restoration, or (2) exogenous estrogen, using a single administration of a pharmacological dose during shock resuscitation. In both ovariectomized and intact mice, hemorrhagic shock induced epithelial cell damages (assessed by KIM-1 renal expression) with secondary renal fibrosis but without significant decrease in GFR at day 21. Ovariectomy with or without estrogen restoration have no significant effect on renal damages and dysfunction. This lack of effect was associated with a marked (> 80%) reduction of total kidney GPR30 expression. By contrast, a single high dose of estradiol in intact mice reduced renal KIM-1 expression by 2/3, attenuated the severity of cell death related to pyroptosis, and prevented the increase of fibrosis by 1/3. This provides a rationale to investigate the benefits of a single administration of estrogen or estrogen modulators during acute kidney injuries in males. Furthermore, the cost/benefit ratio of such administration should be investigated in Human.
Subject(s)
Estrogens/administration & dosage , Kidney/drug effects , Shock, Hemorrhagic/drug therapy , Animals , Female , Humans , Kidney/metabolism , Mice , Mice, Inbred C57BL , Ovariectomy , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Treatment FailureABSTRACT
BACKGROUND: Multiple risk factors for BK polyomavirus (BKPyV) replication after kidney transplantation have been described. Here, we investigated the impact of living donors' urinary BKPyV shedding and recipients' BKPyV antibody status pre-transplant on BKPyV replication during the first year post-transplantation. METHODS: We assessed a cohort of living kidney donors and their paired recipients (n = 121). All donors were tested before transplantation, and recipients were tested before and after transplantation for BKPyV viruria and viremia. BKPyV-specific serology was assessed in all recipients at transplantation. RESULTS: Ten of 121 donors (8.3%) had urinary BKPyV shedding pre-transplant, none had viremia. Overall, 33 (27.3%) recipients developed viruria after transplantation: 7 had received a kidney from a donor with BK viruria (7/10 positive donors) and 26 had received a kidney from a donor without BK viruria (26/111 negative donors; P = .0015). Fifteen (12.4%) recipients developed BK viremia after transplantation: 3 received a kidney from a donor with viruria (3/10 positive donors, 30%) and 12 received a kidney from a donor without viruria (12/111 negative donors, 11%; P = .08). One patient developed proven nephropathy. Ninety-one percent of recipients were seropositive for BKPyV. No relationship between recipients' sero-reactivity at transplantation and post-transplant BKPyV replication was observed. Pre-transplant donor urinary shedding was an independent risk factor for post-transplant BKPyV replication. CONCLUSION: Screening living kidney donors for BKPyV can identify recipients at higher risk for BKPyV replication after transplantation who may benefit from intensified post-transplant screening and treatment strategies.
