## 2 Application of NPs in the Diagnosis of CKD
### Magnetic Resonance Imaging (MRI) Coupled with Nanomaterials  
A great percentage of old patients and patients undergoing angiography experience CKD [66]. The use of gadolinium-based or iodinated contrast agents can exacerbate the disease, or even be fatal [67]. Magnetic NP imaging is a safe strategy that applies superparamagnetic iron-oxide NPs, which are processed and preserved in the hepatic iron reserve of the body and do not influence the kidneys [68].  
The gold standard technique for diagnosing and evaluating renal diseases is currently performed via biopsy since it can only show a connection between the diagnosis of kidney diseases and related pathological alterations. Nonetheless, an invasive method increases the risk of hematoma [69]. Moreover, mismatches between the samples and overall kidney tissue might occur [70]. Therefore, the application of nanotechnology in MRI might diminish the restrictions and be a good substitute for biopsy [71]. In this context, iron oxide NPs are considered as promising surrogates of gadolinium-based MRI contrast agents [72]. These NPs can be utilized not only to assess kidney functions but also to act as cellular imaging apparatuses [73]. The T2-weighted MRI signals have been decreased by using iron oxide particles since these particles can be absorbed by inflammatory cells [74]. The effects of iron oxide injection on the signal intensity of kidneys were assessed in different nephropathic models in rats. The signal intensity loss was observed in the overall components of kidneys in the obstructive nephropathy model nephrotoxic nephritis rate showed a decreased intensity in the cortical signal. This proposes the promising role of iron oxide NPs in detecting different types of renal lesions [75]. Human studies have also shown similar results [76]. Intravenous injection of iron oxide was used to identify and characterize macrophages in infiltrated normal native and transplanted kidneys. A significant signal decrease was shown in the cortical macrophage infiltration; however, patients with ischemic acute tubular necrosis declined the medulla [76]. Since the infiltration of macrophages is a substantial feature of inflammation, a fall in the signal can represent inflammation-related injury. Moreover, different nephropathies could be differentially diagnosed by assessing  
Figure 2: The fluorescence and photoacoustic imaging of Pa-PEG nanodots. (**A**) Fluorescence images. (**B**) Fluorescence signal examination of the tumor. (**C**) Ex vivo fluorescence images of main organs and tumors. (**D**) Photoacoustic images of tumor post injecting Pa-PEG nanodots (**E**) Photoacoustic intensities of localized Pa-PEG nanodots [65].  
the intensity and the area of the MRI signal. Nonetheless, it remains to be clarified if the repeated use of iron oxide NPs induced cytotoxicity, although empirical pharmacokinetic studies and safety assessment have been satisfactory so far [77].  
Hydrophilic MNO NPs with PEG (PEG-MNO NPs) through a polyol-like technique have been developed in a one-pot method. The produced NPs showed a low r2/r1 ratio and high relaxivity. In addition, an acidic environment, glutathione, or exposure to the stimulated body fluid increase the stability of these particles. It has been reported that an amino-modified AS1411 aptamer conjugation with PEG-MNO NPAs can visibly visualize renal carcinoma cells with MRI during in vitro studies which exhibit a more prolonged retention time in the tumor site in vivo in comparison with PEG-MNO NPs [78] (Figure 3).