Chronic kidney disease (CKD) affects over one-tenth of the global population and is associated with increased morbidity and mortality. Patients with CKD often progress to end-stage renal disease (ESRD) and require dialysis and kidney transplantation. Almost all children and over 10% of adult patients who need renal replacement have inherited kidney disease, which makes it one of the five most common causes of ESRD. Causes of CKD in children and young adults differ significantly from those in older individuals.
Recently, we have achieved a deeper understanding of the genetic landscape of CKD in children and young adults through the next-generation sequencing (NGS) technology. Up to the present, about 500 monogenic causes have been successfully identified among patients with CKD. It has been shown that some kind of disease-causing monogenic variants can be detected in nearly 24%-36% of CKD patients. However, monogenic forms of CKD are characterized by high genetic heterogeneity. Thus, a genetic diagnosis is not always possible, even when there is a family history.
It may greatly increase the diagnostic power of genomic sequencing to combine it with transcriptomics analysis of disease tissues. Such combination not only allows validation of variants of unknown significance (VUSs) detected by exome sequencing (ES) and finding new pathogenic variants but also makes it possible to assess the impact of RNA splicing on complex traits and resolve convoluted cases associated with variants that are causative but not detectable by ES, such as intronic variants, repeat expansions, structural variants and etc.. Moreover, all-embracing transcriptome surveys are able to associate alternations of gene expression with varying status and phenotypes of kidney diseases, and to identify novel disease-related pathways and biomarkers. However, the diagnostic utility of transcriptome analyses for renal diseases has not yet been comprehensively evaluated.
Although strong evidence supports a monogenic origin of CAKUT, genetic mutations account for only 10%-20% of all cases. Changes of gene expression that are not caused by DNA sequence variations are usually caused by epigenetic phenomena which include such processes as DNA methylation and histone modifications. Altered epigenetics has been reported in multiple models of CAKUT. During the development of the kidney and urinary system, DNA methylation is highly dynamic, yet orchestrated in a precise spatiotemporal manner. Reasonably, genetics and epigenetics during kidney development and in disease processes are mechanistically intertwined. Thus, epigenetic profiling in CAKUT could offer a powerful strategy to explore the mechanisms behind kidney development and disease processes as well.
We welcome researchers in this field to contribute both Reviews and Original Research articles that address any aspect of the genetics and epigenetics of chronic kidney disease and kidney development. Forum participants are free to champion their insights, hypotheses, fresh data, past research, along future research themes, for the benefit of platform discussion. Topics in the Research Topic may include, but are not limited to:
1) Genetic mechanisms and specific genes involved in the development of chronic kidney disease.
2) Genetic background influences on chronic kidney disease.
3) Epigenetic mechanisms of chronic kidney disease.
4) Genetic and epigenetic interactions.
5) Developmental effects of nutritional or metabolic factors exposure on chronic kidney disease
Chronic kidney disease (CKD) affects over one-tenth of the global population and is associated with increased morbidity and mortality. Patients with CKD often progress to end-stage renal disease (ESRD) and require dialysis and kidney transplantation. Almost all children and over 10% of adult patients who need renal replacement have inherited kidney disease, which makes it one of the five most common causes of ESRD. Causes of CKD in children and young adults differ significantly from those in older individuals.
Recently, we have achieved a deeper understanding of the genetic landscape of CKD in children and young adults through the next-generation sequencing (NGS) technology. Up to the present, about 500 monogenic causes have been successfully identified among patients with CKD. It has been shown that some kind of disease-causing monogenic variants can be detected in nearly 24%-36% of CKD patients. However, monogenic forms of CKD are characterized by high genetic heterogeneity. Thus, a genetic diagnosis is not always possible, even when there is a family history.
It may greatly increase the diagnostic power of genomic sequencing to combine it with transcriptomics analysis of disease tissues. Such combination not only allows validation of variants of unknown significance (VUSs) detected by exome sequencing (ES) and finding new pathogenic variants but also makes it possible to assess the impact of RNA splicing on complex traits and resolve convoluted cases associated with variants that are causative but not detectable by ES, such as intronic variants, repeat expansions, structural variants and etc.. Moreover, all-embracing transcriptome surveys are able to associate alternations of gene expression with varying status and phenotypes of kidney diseases, and to identify novel disease-related pathways and biomarkers. However, the diagnostic utility of transcriptome analyses for renal diseases has not yet been comprehensively evaluated.
Although strong evidence supports a monogenic origin of CAKUT, genetic mutations account for only 10%-20% of all cases. Changes of gene expression that are not caused by DNA sequence variations are usually caused by epigenetic phenomena which include such processes as DNA methylation and histone modifications. Altered epigenetics has been reported in multiple models of CAKUT. During the development of the kidney and urinary system, DNA methylation is highly dynamic, yet orchestrated in a precise spatiotemporal manner. Reasonably, genetics and epigenetics during kidney development and in disease processes are mechanistically intertwined. Thus, epigenetic profiling in CAKUT could offer a powerful strategy to explore the mechanisms behind kidney development and disease processes as well.
We welcome researchers in this field to contribute both Reviews and Original Research articles that address any aspect of the genetics and epigenetics of chronic kidney disease and kidney development. Forum participants are free to champion their insights, hypotheses, fresh data, past research, along future research themes, for the benefit of platform discussion. Topics in the Research Topic may include, but are not limited to:
1) Genetic mechanisms and specific genes involved in the development of chronic kidney disease.
2) Genetic background influences on chronic kidney disease.
3) Epigenetic mechanisms of chronic kidney disease.
4) Genetic and epigenetic interactions.
5) Developmental effects of nutritional or metabolic factors exposure on chronic kidney disease