## 2 Application of NPs in the Diagnosis of CKD
### Kidney Imaging Method Using Fluorescence Nanomaterials  
GFR is a direct indicator of renal function. However, its detection is inconvenient and raises the risk of Iohexol (contrast agents) related-AKI. As mentioned, the CKD-EPI formula is used to calculate GFR. The absorption and secretion of creatinine by tubular cells, which in turn decrease the effectiveness of CKD detection, could be referred to as an important drawback. The application of different fluorescent NPs such as quantum dots, silica, and gold NP offer several advantages in comparison with the conventional method of FGR evaluation. They are entirely filtered by glomeruli, neither induce cytotoxicity nor interfere within body metabolism, are easy to produce, and are cost-effective [54]. Besides, their absorption and emission wavelengths are in the visible (and mainly in the near-infrared) range [55].  
Semiconductor nanocrystals (quantum dots) are among the available commercial fluorescent nanomaterials with extensive applications in biology [56]. Moreover, near-infrared, sensitive, and inexpensive fluorescent imaging has widespread applications in detecting several disorders, including cancer [57]. However, the diagnosis of renal insufficiency and staging via noninvasive fluorescent methods are currently in the preclinical phases [57]. The kidney function has been determined by fluorescent imaging using renal-clearable near-infrared-emitting glutathione-coated gold NPs (GS-AuNPs) as a contrast agent. This method could effectively and noninvasively detect kidney dysfunction, disease stages, and show adaptive functioning in animals with unilateral obstructive nephropathy (UUO). The identification of disease stages was in correlation with the outputs of pathological examinations [58]. Traditional markers of kidney dysfunction (Blood urea nitrogen (BUN) and creatinine) are incapable of determining UUO renal dysfunction. GS-AuNPs induced no structural changes in normal mice kidneys and exhibited a very low concentration in the background tissues [59]. The emission wavelength was approximately 800 nm and thus was visible [60]. Additionally, GS-AuNPs have complete renal removal since their hydrodynamic diameter is lower than the renal filtration threshold [61]. Currently, different renal-clearable NPs such as gold, copper, silica, iron oxide NPs, palladium nanosheets, and quantum dots are available [62; 63]. [PERSON] et al. used silica NPs with fluorescent anti-CD 11b to detect fibrosis and inflammation in a UUO model in vivo [64]. Imaging-guided photodynamic therapy (PDT) with renal clearable ultra-small size NPs has also been a focus of researchers. [PERSON] et al. functionalized Pyrohepophoride-a (Pa), a deep red photosensitizer with polyethylene glycol (PEG), to yield Pa-PEG as ultra-small nanodots which exhibited red-shifted absorbance and efficient singlet oxygen formation upon light irradiation. These Pa-PEG nanodots revealed a significant PDT effect in vitro by attacking many cancer cells. Moreover, Pa-PEG nanodots were used in fluorescence and photoacoustic (PA) imaging methods to determine the optimal period for PDT therapy upon intravenous administration in vivo. An effective accumulation at the tumor site and obtaining the maximum concentration eight hours after injection were noted as the superiorities of this method. Furthermore, the high PA and fluorescent signal from the kidney tissues demonstrated their renal excretion [65] (Figure 2).