Gender Differences in the Acute Kidney Injury to Chronic Kidney Disease Transition

Abstract

This study evaluated if there is a sexual dimorphism in the acute kidney injury (AKI) to chronic kidney disease (CKD) transition and the time-course of the potential mechanisms involved in the dimorphic response. Female and male rats were divided into sham-operated or underwent 45-min renal ischemia (F + IR, and M + IR). All groups were studied at 24-h and 1, 2, 3, or 4-months post-ischemia. Additionally, oophorectomized rats were divided into sham or IR groups. After 24-h, AKI extent was simllar in females and males, but female rats exhibited less oxidative stress and increased renal GSH content. After 4-months and despite similar AKI, the M + IR group developed CKD characterized by proteinuria, tubulointerstitial fibrosis, glomerular hypertrophy, increased oxidative stress and a reduction in HIF1α and VEGF from the 1st-month and persisting throughout the time-course studied. Interestingly, the F + IR group did not develop CKD due to lesser oxidative stress and increased eNOS, TGFβ and HIF1α mRNA levels from the 1st-month after IR. Whereas, oophorectomized rats did develop CKD. We found a sexual dimorphic response in the AKI to CKD transition. Early antioxidant defense and higher TGFβ, HIF1α and eNOS were among the renoprotective mechanisms that the F + IR group demonstrated.

Sex differences in the response to dietary restriction in rodents

“…Females significantly upregulated FGF-21 and its co-receptor, b-Klotho, which controls energy expenditure, while male mice significantly upregulated SIRT-1 with potential renoprotective effects on lipid and glucose metabolism [35]. These sex differences in response to MetR diet may help explain the sexual dimorphism in the acute-to-chronic kidney disease transition [36]. …”

Frequency, Epidemiology and Outcome of Acute Kidney Injury Among Patients Admitted to Nephrology Center, Sana’a: Observational Study

“…It has been reported that AKI is strongly associated with male gender and black race [12]. Several studies have been evaluated whether the risk of AKI, severity, and progression to CKD are influencing by sex but the results are conflicting [18,19]. A recent study found that males are 2.2 times more likely to develop AKI requiring renal replacement therapy [18], conversely another study found the women are more likely to have hospital-acquired AKI [7,20].…”

Integrative View of the Mechanisms that Induce Acute Kidney Injury and its Transition to Chronic Kidney Disease

“…Moreover, it was observed that the female rats had a significant increase in mRNA levels of eNOS, TGF-β, and HIF-1α. A particularly interesting finding was the fact that female oophorectomized rats behaved similarly to male rats; in other words, this group developed CKD 44 . These results strongly suggest the participation of sex hormones in the transition from AKI to CKD.…”

“…Several years ago, it was thought that patients who survived an episode of AKI and who had a recovery of renal function would not have long-term consequences 31 . However, in recent years, this concept has changed based on several experimental and epidemiological studies demonstrating that AKI is a risk factor, leading to progressive kidney disease 7,[32][33][34][35][36][37][38][39][40][41][42][43][44] . In a recent meta-analysis that included 13 previously reported studies in patients who survived an AKI episode, the incidence of CKD and ESRD was 25.8% and 8.6%, respectively 34,35 .…”

“…Several studies have shown that one hallmark of maladaptive repair is the persistence of the inflammatory process, proliferation of fibroblasts, and excessive deposition of extracellular matrix 43,44,[50][51][52][53][54][55][56] . Therefore, the understanding of the mechanisms involved in the AKI to CKD transition will undoubtedly have an impact on the subsequent management of patients who suffered AKI.…”