**10. Diagnosis of Cadmium-Induced Kidney Injury**

While diagnosis of cadmium-induced kidney injury is complicated by factors such as dosage of exposure, duration of exposure, early stage injury or late stage irreversible injury as well as whether there does any exist underlying disease, a series of parameters could be combined to indicate whether a kidney injury is caused by cadmium exposure. These parameters include measurements of blood and urine cadmium, urinary metallothionein, urinary β2-microglobulin and *N*-acetyl-β-glucosaminidase. In addition, kidney injury molecule-1 (Kim-1) could also be used to indicate early stage of cadmium-induced proximal tubular injury [50]. Moreover, severe cadmium poisoning could also cause pains in the spine and joints [24]. Collectively, measurements of these biomarkers or indices should provide good evidence that a cadmium-caused kidney injury has occurred. It should be noted that once these biomarkers appear and are detectable, cadmium induced kidney injury might be at an advanced stage that is irreversible. Therefore, novel biomarkers of cadmium-induced early stage kidney injury remain to be explored.

#### **11. Summary**

Cadmium exposure and cadmium-induced kidney disease are major public health issues. Mitochondria and NADPH oxidase can be impaired by cadmium that accumulates in the proximal tubular site of nephrons, and thus, are the major sources of ROS. Therefore, the main underlying mechanism of cadmium renal toxicity is enhanced oxidative stress and associated damage to DNA, proteins, and lipids, eventually leading to cell death, kidney injury, and decline in kidney function (Figure 5). Given that cadmium exposure is inevitable in the foreseeable future, cadmium-induced animal models of kidney disease should continue to play an important role in investigating the etiological, pathological, pharmacogenetic, pharmacological, and therapeutic aspects of cadmium-induced kidney disorders. Finally, in addition to elucidating the detailed mechanisms of cadmium-caused mitochondrial oxidative stress and redox imbalance, future studies should also explore

novel biomarkers that can be used to diagnose early kidney injury by cadmium exposure. Moreover, whether administration of natural products such as those listed in Table 1 could increase the efflux of cadmium out of the body remains to be investigated.

**Author Contributions:** Conceptulization, L.-J.Y.; original draft preparation, L.-J.Y.; review and editing, D.C.A. and L.-J.Y. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Conflicts of Interest:** The authors declare no conflict of interest.

### **References**

