Advances in the gene therapy of primary hyperoxaluria / 中华泌尿外科杂志

Primary hyperoxaluria (PH) is a rare autosomal recessive hereditary disease, characterized by calcium oxalate kidney stone and nephrocalcinosis caused by defects in enzymes of liver glyoxylate metabolism. Up to now, treatment options for PH are limited. Although medication treatment and liver transplantation can slow down the progression and mitigate the symptoms, the evidence for them turned out to be weak. In recent years, breakthroughs in biotechnology provide novel promising directions for drug development. Small interfering RNA drugs, such as lumasiran and nedosiran, selectively reduce hepatic expression of glycolate oxidase and lactate dehydrogenase respectively, reducing hepatic oxalate production and urinary oxalate levels in PH patients. Gene-editing, such as CRISPR/Cas9, will be a potential treatment method of PH. This review encompasses recent developments in the gene therapy of PH.

Advances of monogenic kidney stone diseases associated with purine metabolism / 中华泌尿外科杂志

Some kidney stones are caused by single gene mutations, and monogenic kidney stone diseases associated with purine metabolic disorder mainly including adenine phosphoribosyltransferase(APRT) deficiency, hypoxanthine-guanine phosphoribosyltransferase(HPRT)deficiency, hereditary xanthinuria(HX), and some diseases caused by gene mutations such as PRS1, SLC22A12, SLC2A9 and ABCG2. Such diseases can lead to abnormal metabolism of purine and uric acid, and then form 2, 8-dihydroxyadenine stones, uric acid stones or xanthine stones. This kind of diseases are rare, the genotype and phenotype of different types of monogenic diseases related to purine metabolism have their own characteristics and are not widely recognized. At present, the main treatment is medical therapy. Gene sequencing will make the diagnosis and find more disease-related genes or mutations. Gene editing, such as CRISPR/Cas9 technology, makes it possible to cure monogenic kidney stone diseases associated with purine metabolism disorder in the future.

Research progress of monogenic nephrocalcinosis / 国际外科学杂志

Nephrocalcinosis is often accompanied by kidney stone disease. In recent years, more and more nephrocalcinosis has been found to be caused by a monogenic disease, and its pathogenesis has not been fully elucidated. With the development of molecular genetics, more than 30 genes have been found to be the causative genes of nephrocalcinosis. At the same time, with the widespread development of genetic testing technology, more patients have received early diagnosis and timely intervention. This article reviews the clinical and basic research progress of monogenic nephrocalcinosis.

Research progress on genotype and phenotype of primary hyperoxaluria / 国际外科学杂志

Primary hyperoxaluria (PH) are important causes of kidney stone and chronic kidney stone disease in children. Recurrent kidney stone disease and nephrocalcinosis should alter the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, the lack of recognition of genotype and phenotype of PH resulted in an unacceptable delay in diagnosis and treatment, sometimes with grave consequences. This paper review the characteristics of genotype and phenotype, genotype-phenotype correlation, current treatment and future gene therapy of PH.

Monogenic nephrolithiasis / 中华实用儿科临床杂志

In recent years, multiple monogenic causes of nephrolithiasis have been identified.Monogenic nephrolithiasis can lead to renal calculus, nephrocalcinosis, extrarenal manifestations, renal insufficiency and renal failure.Advances in genetic testing techniques have improved the ability to obtain a definitive diagnosis of monogenic causes of kidney stone diseases efficiently and effectively.Similarly, advances in gene therapy technologies, especially gene editing, promise to change the way to treat patients with monogenic inherited nephrolithiasis.Now, the classification, cha-racteristics of genotype and phenotype, and the treatment of monogenic causes of nephrolithiasis were reviewed.