Chemotherapy and Its Side Effects: Chapter 3 - Side Effects of Chemotherapy

D. Other Side Effects

D. 2. Kidney damage (nephrotoxicity)

Kidneys play an essential role in the urinary system. In addition, kidneys have other functions, which include the regulation of electrolytes, blood pressure, acid-base balance, re-absorption of glucose & amino acids, and the production of erythropoietin (a hormone that stimulates stem cells in the bone marrow to produce RBCs).

Kidneys filter out creatinine (a break-down product of phosphocreatine in muscle) from blood so that there is little re-absorption of creatinine. Therefore, higher blood levels of creatinine indicate kidney may be injured and has a problem filtering out creatinine. If the filtering function of the kidney is deficient, it usually indicates that significant damage has occurred to normal nephrons (the basic structural and functional unit of the kidney) and blood levels of creatinine will rise. Therefore, creatinine levels in blood and urine may be used to calculate the creatinine clearance as one measurement of renal function.

A more complete kidney function measurement also includes blood urea nitrogen (BUN). Urea is a substance secreted by the liver, and removed from the blood by the kidney. A greatly elevated BUN (>60 mg/dL) generally indicates a moderate-to-severe degree of renal failure.

Unlike conventional drugs, cisplatin is not really “detoxified” by the liver, thus not only can it damage liver, it can also reach the kidney in the same molecular structure and still not easily excreted by the kidneys. As a result, bold levels of creatinine and BUN are usually elevated by cisplatin treatment. 

Nephrotoxicity is the major side effect of cisplatin, which evolves slowly but predictably after initial and repeated exposure of cisplatin. Nephrotoxicity induced by cisplatin may be related to reactive oxygen species (ROS).

In addition, among the earliest reactions of the kidney is the activation of the mitogen-activated protein kinase (MAPK) cascade which is typical of the stress response. The inflammatory cascade is an important determinant of the degree of renal failure induced by cisplatin.

© Jiajiu Shaw, 2020

Disclaimer: This blog is written solely for informational purposes. It does not constitute the practice of any medical, nursing or other medical professional health care advice, diagnosis, or treatment. All contents posted are extracted from the book, "SIDE EFFECTS OF CHEMOTHERAPY AND RADIOTHERAPY", prepared by Dr. Jiajiu Shaw, Dr. Frederick Valeriote, and Dr. Ben Chen.

Chemotherapy and Its Side Effects: Chapter 3 - Side Effects of Chemotherapy

D. Other Side Effects

D.1. Liver damage

Liver is a vital organ and has a wide range of functions. Liver produces bile to aid in digestion through the emulsification of lipids and plays a major role in metabolism. Other functions of liver include hormone production, decomposition of red blood cells (RBCs), plasma protein synthesis, and detoxification of small and complex molecules.

Theoretically, all drugs are associated with certain toxicity (but to different extents) and liver is the major organ that is supposed to “detoxify” the drugs mainly by breaking down the drugs into metabolite(s). The other way for liver to make a drug less toxic is to make it more water soluble, thus more easily excreted out of the body and reduce potential toxicity. However, a small percentage of drugs are able to evade the “protection mechanism” by the liver. In this case, the drugs pass through the body’s major detoxifying guard (liver), damage liver, and move to other organs to exert other side effects.

A typical example of anticancer drugs with potential liver toxicity is cisplatin. Tyrosine kinase inhibitors are also associated with potential liver toxicity. Recently, the FDA required a “black box warnings” to be included on labels of several anticancer drugs to indicate the increased risk of liver injury including some tyrosine kinase inhibitors.

© Jiajiu Shaw, 2020

Disclaimer: This blog is written solely for informational purposes. It does not constitute the practice of any medical, nursing or other medical professional health care advice, diagnosis, or treatment. All contents posted are extracted from the book, "SIDE EFFECTS OF CHEMOTHERAPY AND RADIOTHERAPY", prepared by Dr. Jiajiu Shaw, Dr. Frederick Valeriote, and Dr. Ben Chen.