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Acute kidney injury (AKI) is associated with increased morbidity, prolonged hospitalization, and mortality, especially in high risk patients. Phosphodiesterase 5 inhibitors (PDE5Is), currently available as first-line therapy of erectile dysfunction in humans, have shown a beneficial potential of reno-protection through various reno-protective mechanisms. The aim of this work is to provide a comprehensive overview of the available literature on the reno-protective properties of PDE5Is in the various forms of AKI. Medline was systematically searched from 1946 to November 2019 to detect all relevant animal and human studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. In total, 83 studies were included for qualitative synthesis. Sildenafil is the most widely investigated compound (42 studies), followed by tadalafil (20 studies), icariin (10 studies), vardenafil (7 studies), zaprinast (4 studies), and udenafil (2 studies). Even though data are limited, especially in humans with inconclusive or negative results of only two clinically relevant studies available at present, the results of animal studies are promising. The reno-protective action of PDE5Is was evident in the vast majority of studies, independently of the AKI type and the agent applied. PDE5Is appear to improve the renal functional/histopathological alternations of AKI through various mechanisms, mainly by affecting regional hemodynamics, cell expression, and mitochondrial response to oxidative stress and inflammation.

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Telomeres are specific DNA regions positioned at the ends of chromosomes and composed of functional non-coding repeats. Upon cell division, the telomeres decrease in length by a preordained amount. When the telomeres become critically short, cells lose the ability to divide and enter a specific functioning mode designated as 'cellular senescence'. However, human tissues express an enzyme that deters the shrinking of the telomeres, the telomerase. Due to its ability to maintain telomere length, the telomerase slows down and possibly suspends the aging of the cells. In regard to this, solid evidence demonstrates that female human fertility decreases with increased maternal age and that various adverse factors, including alterations in telomerase activity, can contribute to age-associated infertility in women. The fact that telomerase activity is regulated in a time- and location-dependent manner in both embryo and placental tissues, highlights it potential importance to the successful completion of pregnancy. Since maternal age is a crucial determining factor for the success of in vitro and in vivo fertilization, numerous studies have focused on telomerase activity and its correlation with mammalian fertilization, as well as the following cleavage and pre-implantation developmental processes. Associations between telomerase activity and pregnancy complications have been previously observed. Our aim in this review was to summarize and critically discuss evidence correlating telomerase activity with pregnancy complications.

Graphical abstract

Oxidative stress appears to possess a central role in CIN pathophysiology. Resveratrol (Res) and lycopene (Lyc) are strong natural antioxidants evaluated in a limited number of CIN animal studies in vivo. The aim of the study was to evaluate the potential renoprotective effects of Res/Lyc in a CIN rabbit model. Twenty-four adult male New Zealand white rabbits were equally assigned into four groups: control (saline), CIN (intravenous iopromide; 7.5 g iodine/kg), Res + CIN (per os Res; 5 mg/kg), and Lyc + CIN (per os Lyc; 4 mg/kg). Serum Cr (sCr); symmetric/asymmetric dimethylarginine (SDMA/ADMA); oxidative stress biomarkers: malondialdehyde; total antioxidant capacity; catalase; glutathione) were evaluated in blood samples at three time points: right after (0 h); 24 h; 48 h after iopromide/saline administration. CD20+/CD3+ lymphocytes were determined (48 h). All animals were sacrificed at 48 h and both kidneys collected. Oxidative stress biomarkers were measured in renal tissue. sCr and SDMA/ADMA levels increased significantly in CIN compared to all groups. Oxidative stress secondary to CIN in blood/kidneys was suppressed by Res/Lyc. B and T lymphocytes decreased significantly in CIN compared to all groups. The present study provides emerging evidence that Res/Lyc ameliorate CIN by modulating oxidant/antioxidant balance in blood/renal tissue and by inhibiting vasoconstriction/blood cytotoxicity.

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