Dataset Information

Polymorphism in the GATM Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure.

ABSTRACT: The ten most statistically significant estimated glomerular filtration rate (eGFRcrea)-associated loci from genome-wide association studies (GWAs) are tested for associations with chronic kidney disease (CKD) in 208 patients, including dialysis-independent CKD and dialysis-dependent end-stage renal disease (kidney failure). The allele A of intergenic SNP rs2453533 (near GATM) is more frequent in dialysis-independent CKD patients (n = 135, adjusted p = 0.020) but not dialysis-dependent kidney failure patients (n = 73) compared to healthy controls (n = 309). The allele C of intronic SNP rs4293393 (UMOD) is more frequent in healthy controls (adjusted p = 0.042) than in CKD patients. The Allele T of intronic SNP rs9895661 (BCAS3) is associated with decreased eGFRcys (adjusted p = 0.001) and eGFRcrea (adjusted p = 0.017). Our results provide further evidence of a genetic difference between dialysis-dialysis-independent CKD and dialysis-dependent kidney failure, and add the GATM gene locus to the list of loci associated only with dialysis-independent CKD. GATM risk allele carriers in the dialysis-independent group may have a genetic susceptibility to higher creatinine production rather than increased serum creatinine due to kidney malfunction, and therefore, do not progress to dialysis-dependent kidney failure. When using eGFRcrea for CKD diagnosis, physicians might benefit from information about creatinine-increasing loci.

SUBMITTER: Salamon S

PROVIDER: S-EPMC8228672 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Polymorphism in the GATM Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure.

Šalamon Špela Š Bevc Sebastjan S Ekart Robert R Hojs Radovan R Potočnik Uroš U

Genes 20210528 6

The ten most statistically significant estimated glomerular filtration rate (eGFRcrea)-associated loci from genome-wide association studies (GWAs) are tested for associations with chronic kidney disease (CKD) in 208 patients, including dialysis-independent CKD and dialysis-dependent end-stage renal disease (kidney failure). The allele A of intergenic SNP rs2453533 (near GATM) is more frequent in dialysis-independent CKD patients (n = 135, adjusted p = 0.020) but not dialysis ...[more]

PMID: 34071541

Similar Datasets

Project description:Chronic Kidney Disease (CKD) stands as a substantial challenge within the global health landscape. The elevated metabolic demands essential for sustaining normal kidney function have propelled an increasing interest in unraveling the intricate relationship between mitochondrial dysfunction and CKD. However, the authentic causal relationship between these two factors remains to be conclusively elucidated. This study endeavors to address this knowledge gap through the Mendelian Randomization (MR) method. We utilized large-scale QTL datasets (including 31,684 eQTLs samples, 1980 mQTLs samples, and 35,559 pQTLs samples) to precisely identify key genes related to mitochondrial function as exposure factors. Subsequently, we employed GWAS datasets (comprising 480,698 CKD samples and 1,004,040 eGFRcrea samples) as outcome factors. Through a comprehensive multi-level analysis (encompassing expression, methylation, and protein quantification loci), we evaluated the causal impact of these genes on CKD and estimated glomerular filtration rate (eGFR). The integration and validation of diverse genetic data, complemented by the application of co-localization analysis, bi-directional MR analysis, and various MR methods, notably including inverse variance weighted, have collectively strengthened our confidence in the robustness of these findings. Lastly, we validate the outcomes through examination in human RNA sequencing datasets encompassing various subtypes of CKD. This study unveils significant associations between the glycine amidinotransferase (GATM) and CKD, as well as eGFR. Notably, an augmentation in GATM gene and protein expression corresponds to a diminished risk of CKD, whereas distinct methylation patterns imply an increased risk. Furthermore, a discernible reduction in GATM expression is observed across diverse pathological subtypes of CKD, exhibiting a noteworthy positive correlation with GFR. These findings establish a causal relationship between GATM and CKD, thereby highlighting its potential as a therapeutic target. This insight lays the foundation for the development of potential therapeutic interventions for CKD, presenting substantial clinical promise.

Project description:This article presents a dataset of body composition in chronic kidney disease (CKD) non-dialysis-dependent (NDD), hemodialysis (HD) and peritoneal dialysis (PD) (for at least 3 months), and kidney transplantation (KTx) (for at least 6 months) patients. The data were collected as part of a PhD research project, an observational cross-sectional study followed by a prospective analysis (about 6 months later). Adult CKD patients (18≤age≤60 years old) from a tertiary hospital were recruited: CKD in stages 3b to 5 for NDD patients; PD patients without peritonitis in the last 30 days; HD patients in 4-hour dialysis session, 3 times per week, through an arteriovenous fistula; and KTx patients with CKD in stages 1 to 3a. Patients with presence of amputated limbs or an electronic implant, wheelchair user or inpatient, body weight above 140 kg or BMI higher than 40 kg/m2, acute infections, cancer diagnosis, acquired immunodeficiency syndrome, and others that could alter body composition were excluded. The dataset in this publication consist of some clinical measurements for characterization of the sample, body composition measurements by dual-energy X-ray absorptiometry and by bioelectrical impedance spectroscopy in tetra-polar whole-body wrist to ankle (BISWB) and segmental (BISSEG) protocols of 266 CKD patients, being 137 men and 129 women; 81 in NDD treatment, 83 in HD, 24 in PD, and 80 in KTx. Measurements were performed consecutively by the same professional after an 8-hour fast, empty urinary bladder, drainage of the peritoneal dialysate, and just after the midweek hemodialysis session. To analyze differences among subgroups according to sex and CKD treatment, unpaired T test or ANOVA and Chi-square, adjusted by Bonferroni post-test, were applied. Agreement in fat free mass and fat mass measurements between BISWB and BISSEG, for cross-sectional data and for body composition changes (prospective measurement - cross-sectional measurement), was checked using intraclass correlation coefficient and 95% confidence intervals. Agreement on individual level was evaluated using the Bland-Altman method with limits of agreement. The data can be valuable in the study of body composition in CKD under all types of treatment and also for agreement analysis among body composition measurements by different instruments and techniques. The data are analysed and interpreted in the research article Bellafronte et al., 2020 [1].

Project description:BackgroundOlder adults with chronic kidney disease stage 5 may be offered a choice between dialysis and conservative management. Few studies have explored patients' reasons for choosing conservative management and none have compared the views of those who have chosen different treatments across renal units.Study designQualitative study with semistructured interviews.Settings & participantsPatients 75 years or older recruited from 9 renal units. Units were chosen to reflect variation in the scale of delivery of conservative management.MethodologySemistructured interviews audiorecorded and transcribed verbatim.Analytical approachData were analyzed using thematic analysis.Results42 interviews were completed, 4 to 6 per renal unit. Patients were sampled from those receiving dialysis, those preparing for dialysis, and those choosing conservative management. 14 patients in each group were interviewed. Patients who had chosen different treatments held varying beliefs about what dialysis could offer. The information that patients reported receiving from clinical staff differed between units. Patients from units with a more established conservative management pathway were more aware of conservative management, less often believed that dialysis would guarantee longevity, and more often had discussed the future with staff. Some patients receiving conservative management reported that they would have dialysis if they became unwell in the future, indicating the conditional nature of their decision.LimitationsRecruitment of older adults with frailty and comorbid conditions was difficult and therefore transferability of findings to this population is limited.ConclusionsOlder adults with chronic kidney disease stage 5 who have chosen different treatment options have contrasting beliefs about the likely outcomes of dialysis for those who are influenced by information provided by renal units. Supporting renal staff in discussing conservative management as a valid alternative to dialysis for a subset of patients will aid informed decision making. There is a need for better evidence about conservative management to support shared decision making for older people with chronic kidney failure.

Dataset Information

Polymorphism in the GATM Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure.

Publications

Polymorphism in the <i>GATM</i> Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets