A Systematic Review and Meta-Analysis of Pharmacogenetic Studies in Patients with Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) is an important global public health problem due to its high prevalence and morbidity. Although the treatment of nephrology patients has changed considerably, ineffectiveness and side effects of medications represent a major issue. In an effort to elucidate the contribution of genetic variants located in several genes in the response to treatment of patients with CKD, we performed a systematic review and meta-analysis of all available pharmacogenetics studies. The association between genotype distribution and response to medication was examined using the dominant, recessive, and additive inheritance models. Subgroup analysis based on ethnicity was also performed. In total, 29 studies were included in the meta-analysis, which examined the association of 11 genes (16 polymorphisms) with the response to treatment regarding CKD. Among the 29 studies, 18 studies included patients with renal transplantation, 8 involved patients with nephrotic syndrome, and 3 studies included patients with lupus nephritis. The present meta-analysis provides strong evidence for the contribution of variants harbored in the ABCB1, IL-10, ITPA, MIF, and TNF genes that creates some genetic predisposition that reduces effectiveness or is associated with adverse events of medications used in CKD.

Inappropriate prescribing in patients with kidney disease: A rapid review of prevalence, associated clinical outcomes and impact of interventions

“…Ethnic variation may influence individual responses to medications and susceptibility to specific health conditions associated with CKD. 50,51 The majority of studies in this review were conducted in Western countries. Although no distinct differences in the prevalence of IP across country settings were observed, ethnic factors might contribute to the observed incongruities.…”

“…Ethnic variation may influence individual responses to medications and susceptibility to specific health conditions associated with CKD 50,51 . The majority of studies in this review were conducted in Western countries.…”

The Evolving Role of Diagnostic Genomics in Kidney Transplantation

“…In addition, in future, there may be a role for pharmacogenetics in mainstream practice around transplantation. 28 , 29 , 30 …”

“…In addition, in future, there may be a role for pharmacogenetics in mainstream practice around transplantation. [28][29][30] A situation in which genetic testing should be considered in a potential kidney transplant recipient is when the etiology of the recipient's kidney disease is unclear. In this situation, the recipient should be phenotyped, with the genomic test using either exome sequencing (ES) or genome sequencing (GS).…”

ABCB1 gene polymorphisms impact the effect of high‐dose intravenous methylprednisolone therapy on optic neuritis associated with AQP4‐IgG ‐positive neuromyelitis optica spectrum disorder

“…Recent studies among some populations have confirmed that single nucleotide polymorphisms (SNPs) of ATP binding cassette gene B1 (ABCB1), nuclear receptor subfamily 3 group C member 1 gene (NR3C1), T-cell transcription factor encoding gene (TBX21) and vitamin D receptor encoding gene (VDR) are associated with steroid response. [5][6][7][8] NR3C1 gene encodes the glucocorticoid (GC) receptor, and studies suggested that the lower frequency of NR3C1 rs41423247 polymorphism might contribute to the decreased GC sensitivity in the hypothalamic-pituitaryadrenal (HPA) axis. 6,9 TBX21 gene encodes transcription factors involved in the regulation of developmental processes, including glucocorticoid receptor regulatory network.…”