High Prevalence of Kidney Stones in Asian Jews: Essay Sample

Introduction

Jewish people are Asians where kidney stones are the most prevalent urologic disease in the region. In Asia, the prevalence of kidney stones ranges from 1% to 19.1% (Liu, 2018). The dietary habits, genetics, and climate are the major factors associated with the high prevalence of kidney stones in Asia. In Asia, studies have shown relationship between race and kidney stones where the disease prevalence differ significantly from one race to another (Liu, 2018). Ethnicity has been found to be a potent predictor for disease risk. The frequency of phenotypes and variant alleles vary significantly by ethnic group and this creates differences in expressions of alleles and phenotypes in health and disease. Through epidemiological studies done in Asia, it has been found that various countries in the region have family members with family history of kidney stones. In this regard, genetics and the ethnicity of a patient are crucial in clinical examination and pharmacology. This relationship between the genetics, ethnicity and kidney stones makes the 29-year-old Jewish male patient relevant to the study.

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The Relevance of the Patient's Diet (Epigenetics)

Dietary habits have been found to play a critical role in formation of kidney stones. Westernized diets are rich in excessive protein, calcium, lipid and sodium which are potent factors for development of kidney stones (Liu, 2018). As a result, the Asian countries have been found to consume food is rich in oxalate which causes stones in the kidney. Dietary habits affect and stimulate epigenetic modifications. Dietary habits introduce varied nutrient amounts which in turn modify the physiological processes via epigenetic mechanisms. This further affects the regulation of gene activity and disease occurrence and progression. Therefore, since modification of physiological processes takes place through epigenetic mechanisms, it becomes the patient's diet relevance in the study. Contribution of Animal studies to Understanding of Kidney Stones

Animal studies have been used over time to mimic the biological processes that take place in the human body. Although there are inherent differences between the kidneys of rats and humans, the cortex-medulla ratio (2:1) of a rat resembles that of humans and this makes it significant to develop animal models to study and understand the stone pathogenesis (Tzou, Taguchi, Chi & Stoller, 2016).

Clinical Research Studies and Animal Studies

Various clinical studies such as Tzou, Taguchi, Chi and Stoller (2016); have supported the conclusions from animal studies. A consensus has been developed regarding genetic, epigenetic and medical intervention factors Zisman (2017).

Biochemistry of Kidney Stones and its Resolution

The metabolism of every food type in the body undergoes unique pathways to produce specific end products under suitable conditions. The food breakdown process is aided by enzymes that are specific for the metabolism of certain food types in the body. Proteins are broken down by specific enzymes, and so are other food types. Appendix 1 shows a chain of reactions that take place when collagen jello which is rich in glycine undergoes a series of processes in the body upon consumption. Jello is digested into glycine, which is then oxidized to glycine imine, which is further hydrolyzed into glyoxylate and ammonia and later oxalate.

In human beings, the source of glyoxylate is glycolate, glycine, hydroxyproline, and glyoxal among other amino acids (Knight, Easter, Neiberg, Assimos, & Holmes, 2009). Glyoxylate acts as a metabolism intermediary and is a two-carbon keto -acid. Through dehydrogenases and oxidases process, it is converted into oxalate. On the other hand, glycine plays roles in the body such as acting as the precursor of purines, 1-carbon units and proteins (Lamers, 2009). The breakdown of glyoxylate is aided by the glyoxylate aminotransferase. According to Pey, Albert, and Salido (2013), the coenzyme alanine-glyoxylate aminotransferase is responsible for catalyzing the transmission between glycine, and pyruvate to glyoxylate and L-alanine. When the enzyme alanine-glyoxalate aminotransferase (AGT) is absent during the metabolism process, the person develops primary hyperoxaluria type 1 (Pey, Albert, & Salido, 2013). When a person takes a diet rich in glyoxylate in the absence of vitamin B6, there is a likelihood of developing severe hypocitraturia or hyperoxaluria (Nishijima, 2006). Oxalate is a toxin in the body since it precipitates as tissue-damaging calcium oxalate, hence it has to be excreted through urine. In this regard, the detoxification process of glyoxalate in the human body is essential. A normal oxalate excretion level is below 0.5 mmoL/1.73 m2. Hence any level above 5 mmoL is too high.

It has been established through research that vitamin B6 is essential in the metabolism of glyoxylate (Nishijima, 2006). Vitamin B-6, which is otherwise known as pyridoxal 5'-phosphate (PLP), is used as a cofactor in the metabolism of glyoxalate. Nishijima (2006) examined the role played by vitamin B-6 in the metabolism of glyoxalate and hepatic alanine in rats. The study divided male rats into a vitamin B6 free diet and glyoxalate water group, control group, glyoxalate water group, and vitamin B-6 deficient diet. The study found a high oxalate/creatinine ratio in three groups, and high glycolate/creatinine ratio in the groups without vitamin B-6, although the control group had low levels. However, the study found that the glycine/creatinine ratio was low in the two groups without vitamin B-6. Conversely, the levels of hepatic AGT mRNA was low in groups without vitamin B-6 but higher in the control group and glycolate water group. From these results, it can be deduced that glyoxalate metabolism requires vitamin B-6 as a coenzyme of AGT. At high levels of glyoxylate intake, the vitamin B-6 is highly needed. The deficiency of vitamin B-6 leads to severe hyperoxaluria. These findings have been supported by Runjan and Gershoff (1964) who established that deficiency of vitamin B-6 in rats, monkeys, and cats are associated with an increment in the excretion of endogenous urinary oxalate.

Due to the presence of glyoxalate reductase activity in the kidney, the glyoxalate can be converted back to glycine. However, the kidney has AGT2 activity whose affinity for glyoxalate is lower compared to AGT1 (Knight et al., 2006). For kidney to facilitate such conversion, AGT1 is a requirement since it has a higher affinity. Besides, since the conversion rate is very slow, the conversion of glycine into glyoxalate outweighs the reverse conversion. Hence, its lack hinders the conversion of glyoxalate to glycine and this facilitates more formation of oxalate hence escalating the kidney problem.

According to Zisman (2017), the intervention options for Nephrolithiasis are classified into pharmaceutical therapies and lifestyle interventions. The lifestyle interventions entail the use of targeted dietary modifications and increased fluid intake. Examples include dietary interventions such as calcium intake and low intake of oxalate, protein, and sodium-rich foods. If the lifestyle interventions are not sufficient, the pharmaceutical therapies such as alkali salts, uric acid-lowering agents, citrate salts and thiazides are used (Zisman, 2017).

References

Knight, J., Easter, L. H., Neiberg, R., Assimos, D. G., & Holmes, R. P. (2009). Increased protein intake on controlled oxalate diets does not increase urinary oxalate excretion. Urological Research, 37(2), 63-68. DOI:10.1007/s00240-009-0170-z

Lamers, Y., Williamson, J., Ralat, M., Quinlivan, E., Gilbert, L., Keeling ...& Gregory, J. (2009). Moderate Dietary Vitamin B-6 Restriction Raises Plasma Glycine and Cystathionine Concentrations While Minimally Affecting the Rates of Glycine Turnover and Glycine Cleavage in Healthy Men and Women. The Journal of Nutrition, 139(3), 452-460. DOI: 10.3945/jn.108.099184

Liu, Y., Chen, Y., Liao, B., Luo, D., Wang, K., Li, H., & Zeng, G. (2018). Epidemiology of urolithiasis in Asia. Asian Journal of Urology, 5(4), 205-214. DOI:10.1016/j.ajur.2018.08.007

Nishijima, S., Sugaya, K., Hokama, S., Oshiro, Y., Uchida, A., Morozumi, M., & Ogawa, Y. (2006). Effect of vitamin B6 deficiency on glyoxylate metabolism in rats with or without glyoxylate overload. Biomedical Research, 27(3), 93-98. DOI: 10.2220/biomedres.27.93

Pey, A. L., Albert, A., & Salido, E. (2013). Protein homeostasis defects of alanine-glyoxylate aminotransferase: new therapeutic strategies in primary hyperoxaluria type I. BioMed research international, 2013, 687658. DOI:10.1155/2013/687658

Runyan, T., & Gershoff, S. (1965). The Effect of Vitamin B, Deficiency in Rats on the Metabolism of Oxalic Acid Precursors. The Journal of Biological Chemistry, 240(5). Retrieved from https://pdfs.semanticscholar.org/6afb/6767595dc7f482fbd1767d70b137dce00d82.pdf?_ga=2.257343371.1438465190.1567082852-1871163874.1566280296

Tzou, D., Taguchi, K., Chi, T., & Stoller, M. (2016). Animal models of urinary stone disease. International Journal of Surgery, 36, 596-606. DOI: 10.1016/j.ijsu.2016.11.018

Zisman, A. (2017). Effectiveness of Treatment Modalities on Kidney Stone Recurrence. Clinical Journal of the American Society Of Nephrology, 12(10), 1699-1708. DOI: 10.2215/cjn.11201016