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Innovative Medicines & Omics Current approach in the management of kidney disease

atrophic as a result of aberrant repair pathways. Pro- aerobic metabolism and increased oxidative stress in
fibrotic cytokines, including connective tissue growth patients receiving hemodialysis and those with CKD.
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factor and transforming growth factor-β (TGF-β), may be The etiology of CKD is influenced by hampered cellular
produced by G2/M-arrested TECs through activation of antioxidant mechanisms, which also affect signaling
JNK signaling. Cell cycle arrest may dictate the course of processes that lead to senescence and death of renal cells,
damage, whereas favorable cell cycle events may determine renal fibrosis, and reduced renal cell regeneration.
the healing. Dysregulated and inefficient tubular repair This review gives an update on the discovery of new
has been associated with the converging of tubular cells antioxidant drugs for CKD and discusses the sources of
toward a pro-fibrotic and senescent phenotype, sustained ROS, transcription factors, and signaling mechanisms
inflammation, and ECM deposition. 2,3 impacted by the oxidative stress-related pathway during the
It has been noted that regardless of the cause, patients development of renal fibrosis. Ongoing research worldwide
with AKI are more likely to develop CKD, end-stage renal is exploring various causes of KD and contemporary
disease (ESKD), and premature mortality. At present, 850 prevention measures (Figure 1), which are outlined in this
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million individuals are suffering from KD and its related review article.
illnesses, including the 3.9 million receiving regular dialysis
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or kidney transplantation. Globally, the anticipated 2. Newly identified causes of CKD
number of individuals with diabetes in 2015 was 415 2.1. Mitochondrial dysfunction
million, or 8.8% of the total population. This is more than Despite the fact that mitochondria have long been
double the 4.6% (151 million) estimated in 2000, and by
2040, the figure is predicted to rise to 10.4% (642 million). associated with the pathobiology of AKI, interest in how
One well-known example of a chronic multisystemic this cellular organelle contributes to the development of
AKI and CKD is expanding. Mitochondrial fragmentation
illness linked to an increased risk factor of CVD is CKD. has been related to cell loss in the kidney and other organs.
According to clinical and experimental evidence, CKD The mitochondrial fission protein dynamin-related protein
increases oxidative stress and promotes an inflammatory 1 (DRP1), which constricts and cleaves mitochondria and
state, both of which are critical factors in the development induces fragmentation, was specifically deleted in the
of CVD in uremia. 6,7
proximal tubules, preventing renal ischemia-reperfusion
CKD is marked by vasculopathy, renal interstitial damage and promoting epithelial recovery. Furthermore,
fibrosis, tubular atrophy, and glomerulosclerosis, DRP1 deletion in the proximal tubules after ischemia-
leading to impaired kidney regeneration. Renal fibrosis reperfusion slowed the development of kidney damage
is histologically indicative of the onset of KD, albeit the and fibrosis, suggesting that DRP1 in the proximal tubules
underlying mechanisms are yet unknown. Over the increases the kidneys’ vulnerability to AKI and that
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last few decades, research on animals and molecules activation of the protein contributes to maladaptive repair
has expanded our knowledge of the pathophysiology of over time. 11,12
AKI, identifying oxidative stress, endothelial damage,
mitochondrial injury, and innate immunity as primary 2.2. Cell death pathway
causes. Oxidative stress is thought to be a major factor in The control of cell death is another crucial function
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the development of endothelial impairment, as excessive of mitochondria, in addition to their well-known
reactive oxygen species (ROS) activate intracellular involvement in cellular metabolism. Recent research
signaling pathways, such as mitogen-activated protein suggests that mitochondrial permeability transition is
kinase (MAPK). Furthermore, the uremic endothelium also an important mediator of AKI and the subsequent
exhibits a proinflammatory phenotype, characterized progression to CKD. These pathways include necroptosis,
by increased synthesis and expression of adhesion ferroptosis, and apoptosis. Studies have shown that the
molecules, which have been found to be important factors absence of caspase-3, a key pro-apoptotic enzyme, leads
in endothelial activation and damage. Many signaling to significant kidney abnormalities in mice, highlighting
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pathways that maintain homeostasis are routinely activated the critical role of tubular cell death in AKI. Recent
by the creation of reactive species. However, the excessive research suggests that ischemic conditions lead to
generation of reactive species can be highly detrimental. reduced microvascular loss in mice but exacerbate tubular
As mitochondrial damage increases, the electron transport damage, accompanied by elevated levels of the necroptosis
chain becomes less effective, which also results in a drop in marker, receptor-interacting protein kinase 3 (RIPK3).
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ATP production and an increased ROS creation. Impaired Ischemia induces apoptosis by causing oxidative stress,
mitochondrial respiration is an indication of an imbalanced mitochondrial dysfunction, and the production of

Volume 2 Issue 1 (2025) 37 doi: 10.36922/imo.4969