Pregnancy protects the kidney from acute ischemic injury

Abstract

A complex analysis of acute kidney injury (AKI) in pregnant women shows that it is caused by the interaction of gestation-associated pathologies and beneficial signaling pathways activated by pregnancy. Studies report an increase in the regeneration of some organs during pregnancy. However, the kidney response to the injury during pregnancy has not been addressed. We investigated the mechanisms of the pregnancy influence on AKI. During pregnancy, the kidneys were shown to be more tolerant to AKI. Pregnant animals showed remarkable preservation of kidney functions after ischemia/reperfusion (I/R) indicated by the decrease of serum creatinine levels. The pregnant rats also demonstrated a significant decrease in kidney injury markers and an increase in protective markers. Two months after the I/R, group of pregnant animals had a decreased level of fibrosis in the kidney tissue. These effects are likely linked to increased cell proliferation after injury: using real-time cell proliferation monitoring we demonstrated that after ischemic injury, cells isolated from pregnant animal kidneys had higher proliferation potential vs. control animals; it was also supported by an increase of proliferation marker PCNA levels in kidneys of pregnant animals. We suggest that these effects are associated with hormonal changes in the maternal organism, since hormonal pseudopregnancy simulated effects of pregnancy.

Mechanisms of Age-Dependent Loss of Dietary Restriction Protective Effects in Acute Kidney Injury

“…We assessed the proliferative capacity of primary cultures of RTCs obtained from young and old kidneys by the real-time monitoring of the cell growth rate ( Figure 5 A). The analysis was performed by using iCELLigence, which has already been used for studying proliferation and the death of RTCs [ 32 ]. We found that RTCs isolated from the kidneys of young rats characterized by a more rapid growth rate exceeding the growth of old cells by more than 4 fold ( Figure 5 B).…”

“…Analysis of cells growth kinetics was performed using an RTCA iCELLigence™ instrument (ACEA, San Diego, CA, USA). This method is based on using electrical impedance of cell-covered electrodes [ 31 ] and may be used in particular for studies of RTCs proliferation and death [ 32 ]. The iCELLigence RTCA instrument was placed in a humidified incubator at 37 °C and 5% CO 2 .…”

Acute kidney injury during pregnancy leads to increased sFlt-1 and sEng and decreased renal T regulatory cells in pregnant rats with HELLP syndrome

“…There are very few actual models of pregnancy-related AKI. One exception is the model of AKI by Popkov et al in which pregnant rats underwent unilateral IR on gestational day 18 for 40 min [ 21 ]. The study of kidney injury during hypertensive pregnancies such as HELLP syndrome and preeclampsia is important for understanding the mechanisms involved in both the short- and long-term adverse consequences associated with these disorders [ 5 ].…”

“…In this study, we found that NP+AKI rats as well as HELLP+AKI rats also had significant evidence of kidney damage (increased KIM-1, BUN, and creatinine, and decreased urine output) compared to NP rats, which was accompanied by decreased T regulatory cells and decreased sEng. While in the current study we only examined pregnant animal models, it should be mentioned that it has been suggested that the effects of IR on the kidney during pregnancy are less severe compared to what occurs in the non-pregnant state, suggesting that pregnancy increases the tolerance of the kidneys to AKI [ 21 ]. Examining AKI in non-pregnant rats is out of the scope of the current study; therefore, we cannot refute this claim.…”

“…On gestational day (GD) 12, mini-osmotic pumps (model 2002, Alzet Scientific Corporation, Cupertino, CA) were inserted into a subset of normal pregnant rats (NP) to allow infusion of sFlt-1 and sEng (4.7 and 7 μg/kg, respectively, R&D Systems, Minneapolis, MN) as previously described to induce the HELLP syndrome phenotype [ 15 , 16 , 20 ]. In the current study, we induced AKI by IR, since it has been reported to consistently induce AKI in experimental pregnant and non-pregnant animal models [ 21 , 22 ]. To induce AKI, on GD18, a subset of NP ( n = 18) and HELLP rats ( n = 20) were anesthetized with isoflurane and placed on an AIMS™ Thermo-controlled surgical platform prior to an abdominal midline incision being made to expose the kidneys.…”