Kulvinder Kochar Kaur *, Gautam Nand K Allahbadia, Mandeep Singh
As we all know Diabetic Kidney Disease (DKD) represents the commonest etiology for Chronic Kidney Disease (CKD) along with end-stage renal Disease (ESRD). Earlier we have reviewed in detail the role of epigenetic modifications in the case of DKD and the medications undergoing trial regarding that like Apabetalone, Apelin, curcumin analogs, sodium, butyrate, the role of bromodomain extra terminal (BET) Proteins, roles of different histone acetylases like KDM6A (alias UTX), enhancer of Zeme Homolog 2 (EZH2) methylases, besides how to avoid propagation of CKD in general. As far as the natural history of DKD goes it is inclusive of glomerular hyperfiltration, propagative albuminuria along with reducing glomerular filtration rate (GFR), and finally renal failure.
We already possess the information that DKD is correlated with metabolic alterations that occur secondary to hyperglycemia causing glomerular hypertrophy, glomerulosclerosis, tubulointerstitial inflammation as well as fibrosis. Here we have updated other etiological factors like part of the Cannabinoid receptor (CB1) in DKD, and the role of Pyroptosis that is further being explored, along with an update regarding how hyperglycemia brings about epigenetic modifications.
Initially, it was believed that with the advent of sodium–glucose cotransporter 2 (SGLT2) inhibitors both cardiovascular outcomes (CVOT) as well renal outcomes improved. Nevertheless, all of these are efficacious just if an early diagnosis of DKD is made, however, nothing works in avoidance of the propagation of DKD. Numerous trials are going on with regards to Bardoxolone Methyl Treatment along with credence trials regarding Canagliflozin, positive actions of incretins might be renoprotective.
Further Hypoxia-inducible factor prolyl hydroxylaseampering agents having been approved for renal anemia are undergoing trials. Moreover, certain ACE2 inhibitors or angiotensin blockers are being worked out. Once it is realized which of these drugs works then the combination of SGLT2 inhibitors can be tried with proven positive actions of these drugs.