Urolithiasis incidence and prevalence have been on a rise. Kidney stone disease is a very painful disease in some cases and might go unnoticed in some others. Kidney stones are formed due to the precipitation of certain minerals in the urine. They may vary in size, color, and shape depending on the material they are composed of. The intensity of the pain depends majorly on the size and shape of the stone. The stone may pass naturally or may require medical interventions based on the above factors. Certain factors can increase the risk of getting urinary calculi in a lifetime. One very important risk factor that has been seen to be explicitly associated with cases of kidney stones is the history of occurrence of kidney stones, either personal or in the family.
A personal history of kidney stone means the recorded case of one or more kidney stone incidents. The presence of positive family history means having a family member or more who have gone through an episode or more of kidney stones. Personal or family history of kidney stones is strongly associated with an increased risk of kidney stones. Genetic factors play an important role in risk associated with family history and personal history. Other genetic conditions such as defective oxalate transport, hypercalciuria, hyperuricemia, defective oxalate transport, incomplete renal tubular acidosis may predispose a patient to formation of kidney stones.
A personal or family history would mean a high probability of some genetic changes that influence metabolism. Genes that are involved in transmission of chemical signals have an important role in the pathogenesis of this disease. These genes also play a role in transportation of materials in and out of cells that help to regulate levels of minerals and other components inside the cells. Any mutation in these genes can result in altered levels of contents inside and outside of the cells that can lead to imbalance of compounds in the urine, consequently increasing the risk of stone formation. Error in metabolism may also lead to increased dehydration, a condition which can influence stone formation critically. These changes may be due to complete loss of an enzyme or a protein involved in transport that leads to accumulation of insoluble compounds or a mutation that has an indirect effect and may predispose the patient to stone formation, for example- renal tubular acidosis..
Currently, 30 genes are known to be involved in kidney stone formation. The gene mutations in SLC7A9 that cause cystinuria are most commonly found in patients with kidney stone disease. Another set of genes important in the disease is APRT and XDH that are involved in purine metabolism. If a problem is present in these genes, even renal transplant can’t help correct the situation of renal failure. Deficiency of genes AGXT, GRHPR, HOGA1 lead to metabolism of cellular compounds to calcium oxalate that can precipitate and form stones. Calcium oxalate precipitation can also occur due to mutations in SLC26A1 along with hyperoxaluria. SLC3A1 and SLC7A9 encode transporters of cysteine. Errors in these genes would lead to cystinuria causing excretion of high levels of cystine, arginine, ornithine, and lysine in urine. Research in the future might reveal more genes and pathways that participate in calculi formation in cases of personal and family history. This would give us a clearer understanding of the role of personal/family history in the pathogenesis of kidney stone disease.
