## 2 Application of NPs in the Diagnosis of CKD
### Detection of Kidney Injury Biomarkers
In a similar report, KIM-1 was detected via an ECL biosensor in which Pt NPs were used to enhance the electron transfer efficiency [41]. Therefore, nanotechnological advances can pave the way to yield an effective and sensitive detection method for CKD, which in turn will facilitate earlier intervention. MicroRNAsNAs (miRNAsRNAs) as short single-stranded RNAs, regulate the expression of genes that are paired with regions within the 3'-urntranslated region of target mRNAs [44; 45]. The current research highlights the role of small non-coding RNAs in the pathophysiology of renal diseases since the potential role of miRNAs as renal disease biomarkers are gaining increasing attention [46; 47]. However, the standardization of measuring methods is required in order to validate the efficiency of these biomarkers. Moreover, selecting the appropriate tissue or biofluid is essential to achieve ideal results in clinical settings. The expression levels of miRNAs involved in kidney disease might represent novel treatment approaches [48]. The bioavailability and activity of insulin-like growth factor (IGF) are mediated by a number of superfamily members of homologous proteins referred to as insulin-like growth factor binding proteins (IGFBPs). Given the pivotal role of these proteins, IGFBP 7 has been reported as a possible independent biomarker of AKI with high specificity and sensitivity [49]. Similarly, IGFBP 2 has been connected with the kidney through the elevation of reactive oxygen species-related apoptosis in the renal tubular epithelium [50], hinting to the  
Figure 1: Schematic illustration of systematic protocol for immunosensor fabrication and operation. Screen-printed carbon electrode (SPCE) interdigitated on a flexible plastic substrate (**a**). SPCE have modified with gold nanoparticles (SPCE/Au NCs) (**b**). Polystyrene nanoparticle core with silver nanoshells (PS-Ag) covalently conjugated to Human Serum Albumin (HSA) antibodies and these nanoprobes are trapped on the electrode surface (PS/Ag/ab-HSA nanoprobes) (**c**). In order to perform immunosensing, HAS protein was dropped onto the sensing areas (**d**). PS-Ag nanoparticles improved surface areas and incresed the number of immobilized antibodies (**e**). Immunosensing results with normalized impedance response, good linearity and repeatability dependent on albumin concentration (**f**). (Reprinted with permission from Ref. [34] Copyright © 2018 Elsevier B.V.). potential role of this molecule as a kidney damage biomarker [51; 52]. Therefore, detecting IGFBPs with novel and rapid techniques might shed new light to the early treatment of renal diseases. [PERSON] and coworkers analyzed the blood serum of renal cell carcinoma (RCC) patients via laser desorption/ionization mass spectrometry on a gold nanoparticle-enhanced target (AuNPET) approach. This study led to the identification of potential biomarkers of RCC such as creatinine, dihydroouracil, melatonin, palmitoyl glucuronide, tyrosine, and glutamine. The applied nanotechnology-based MS detection method was successful in identifying the metabolic biomarkers of RCC [53].