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

Progressive renal insufficiency has been associated with 3.5. Janus kinase inhibitors and signal transducer
decreased tryptophan levels and kynurenine accumulation and activator of transcription (JAK/STAT) inhibition
due to inflammation and impaired kidney function in JAK and STAT are important intracellular mediators
diabetic individuals. Proteinuria and albuminuria are of growth hormone, erythropoietin, pro-epidermal
signs of several kidney illnesses, and a few clinical and growth factor, and inflammatory cytokines such as
experimental studies have looked into the potential link interleukin(IL)-6, IL-23, IL-12, interferon, and its cognate
between the kynurenine pathway and these conditions. receptor. According to recent clinical trials, autoimmune
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Kynurenine aminotransferases are the enzymes inflammatory diseases such as rheumatoid arthritis and
responsible for converting kynurenine into its downstream ulcerative colitis can be effectively treated with JAK
metabolites, and RAS inhibitors can reduce their activity, inhibitors such as tofacitinib and baricitinib. In diabetic
hence reducing the synthesis of kynurenic acid in kidney KD, the JAK/STAT signaling pathway and the documented
homogenates. These findings could be clinically significant clinical anti-inflammatory activity of JAK inhibitors have
because kynurenic acid has been linked to the extent prompted a Phase II investigation to assess their clinical
of renal function loss in patients with kidney illness. effectiveness in renal illness. In this trial, patients with
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However, recent research has shown that RAS inhibitors proteinuria in diabetic KD who were already on ACEIs
may cause common adverse effects such as anemia, and ARBs were treated with the JAK1 and JAK2 inhibitor
hyperkalemia, and functional renal insufficiency. 41 baricitinib for 24 weeks. The results showed a 30 – 40%
reduction in albuminuria with baricitinib treatment.
3.3. Anti-inflammatory therapy However, a side effect associated with this class of drugs
Renal failure in individuals with diabetes and inflammation – decreased hemoglobin level – was observed. The extent
has long been linked. Growing evidence from both animal to which these effects on albuminuria decreased translate
and clinical trials suggests that endothelin Type A receptor into long-term advantages for renal function and mortality
antagonists may have a role in the treatment of diabetic remains to be determined. 45,33
renal diseases (DRD). Vasoconstriction, mesangial 3.6. Apoptosis-based treatment strategies in AKI
proliferation, podocyte damage, inflammation, and fibrosis
are all linked to increased renal endothelin expression Recent research indicates that a variety of pathways
in DRD. In DRD patients, the expression of endothelial contribute to both apoptosis and programmed necrosis-
adhesion molecules such as intercellular adhesion molecule induced cell death following apoptosis, including in
1 (ICAM-1), vascular adhesion protein 1 (VAP-1), and AKI. Suppressing both processes may be necessary to
vascular cell adhesion protein 1 (VCAM-1) is increased, completely avoid AKI. This is noteworthy because caspase
and this increase is associated with the severity of the inhibitors may affect autophagy and proinflammatory
illness. These molecules are crucial for leukocyte adhesion necroptosis, two other processes involved in cell death
to the endothelium; therefore, blocking them may affect and survival. Phosphorylation and activation of p53 have
a major function in the pathogenesis of vancomycin-
leukocyte trafficking and reduce inflammation in DRD. 42
induced AKI, as well as nephrotoxicity caused by folic
3.4. TNF inhibition acid, aristolochic acid, and cisplatin. Ferroptosis, cell
cycle arrest, autophagy, metabolism, fibrosis, and
The results are consistent with previous research suggesting both necrotic and apoptotic cell death are among the
that in diabetes, hyperglycemia-induced formation processes in which p53 is implicated in the kidney. Based
of advanced glycation end-products (AGEs) triggers on experimental studies, the protection against ischemia
macrophage production of TNF. However, it is unknown and cisplatin-induced AKI is due to the pharmacological
whether TNF or its receptors play harmful functions in suppression or proximal tubule-specific p53 deletion. 46,47
the development of KD and diabetic nephropathy. TNF The p53 gene is targeted by a small interfering RNA
receptor-deficient animals treated with TNF-neutralizing known as teprasiran, and in a randomized Phase 2
antibodies have lessened disease severity in experimental clinical trial, teprasiran provided protection against
rodent models of renal disease. Despite anti-TNF drugs AKI in high-risk, on-pump patients undergoing heart
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being used clinically for more than 20 years, few studies surgery. 48
have looked into their clinical activity in renal illness. Such
studies have been limited in size and mostly concentrated 3.7. Phytomedicinal therapeutic approach of KD
on focal segmental glomerulosclerosis and lupus nephritis, Phytocompounds are naturally occurring groupings of
leaving their potential involvement in various types of different substances that are present in plants and fruits
CKD development largely unanswered. that have several health-beneficial effects, including anti-

Volume 2 Issue 1 (2025) 41 doi: 10.36922/imo.4969