## 4 Discussion  
The key findings of this study are that all six novel whole blood miRNAs were significantly associated with prevalent CKD, independent of conventional risk factors. The expression profile of miRNAs ( hsa-miR-novel-chr1_36178, hsa-miR-novel-chr2_55842, hsa-miR-novel-chr7_76196, hsa-miR-novel-chr5_67265, and hsa-miR-novel-chr13_13519) were significantly higher in CKD individuals as compared to those with normal kidney function. While all the miRNAs had acceptable and comparable discriminatory power for prevalent CKD, only hsa-miR-novel-chr13_13519 added to predictions beyond conventional risk factors. The findings of the current investigation suggest that these novel whole blood miRNAs have a potential to contribute to CKD risk screening in people with HTN and/or DM. Various studies have reported on the dysregulated patterns of miRNAs in CKD in individuals with HTN and DM. [PERSON] et al. were among the first to demonstrate the role of miRNAs in the development of diabetic kidney disease (DKD) [21; 33]. They showed that the expression of miR-192 was significantly elevated in the glomeruli of a diabetic mouse model [21] and, in a further study, showed that miR-192 induced the transforming growth factor beta 1 (TGF-\(\beta\)1) signaling, accelerating the progression of DKD [33]. Another study explored the expression profile and clinical significance of plasma miRNAs in Chinese individuals with DKD and found that the expression profiles of miR-150-5p, miR-155-5p, miR-30e, miR-320e, and miR-3196 were significantly decreased during the early stages of DKD [23]. A study performed in Egyptians with type 2 DM showed that levels of miR-451 were elevated and reduced in plasma and urine samples, respectively, in different stages of DKD [34]. Studies by [PERSON] et al. demonstrated that downregulation of miR-214-3p may be associated with the development of chronic kidney injury in HTN, and showed that upregulation of this miRNA may offer a protective role in the kidneys [35; 36]. A study by [PERSON] et al. showed that serum- and urine-derived miR-103a-3p were significantly higher in individuals with hypertensive nephropathy and hypertensive mice infused with angiotensin II hormone compared to normal controls. The authors found that this hormone-induced kidney injury via the activation of the SNRK /NF-kB/p65 signaling pathway and was positively associated with increased levels of miR-103a-3p [37]. [PERSON] et al. recently examined the expression profile of let-7g-5p and miR-191-5p in platelet-poor plasma and found that the decreased levels of these miRNAs were independently associated with CKD among individuals with HTN. This, therefore, suggested that let-7g-5p and miR-191-5p may be involved in the pathophysiology of CKD and may serve as potential biomarkers for disease diagnosis [38]. In the current study, we observed that increased expression of hsa-miR-novel-chr2_55842 and hsa-miR-novel-chr7_76196 were independently associated with reduced eGFR, similar to other studies that reported a positive association with eGFR, albeit with other miRNAs [23; 38]. However, the association between hsa-miR-novel-chr5_67265 and hsa-miR-novel-chr13_13519 and eGFR was influenced by smoking. Previous studies, like the one by [PERSON] et al., likewise found that exposure to cigarette smoke mediated the regulation of certain miRNAs. In their case, miR-155 and miR-21 were upregulated and the expression of miR-126-3p was downregulated [39]. Moreover, the current study showed that all six novel miRNAs were positively associated with prevalent CKD in individuals with HTN and/or DM, independent of conventional risk factors, like age and gender. Furthermore, all six novel miRNAs had an acceptable ability to predict CKD (AUC > 0.7). However, the prediction model containing hsa-miR-novel-chr13_13519 offered an additional advantage in predicting CKD, above that of conventional risk factors (age, gender. smoking status, drink status, DM, and HPT status).