Molecular aspects and long-term outcome of patients with primary distal renal tubular acidosis

Gómez-Conde, Sara; García-Castaño, Alejandro; Aguirre, Mireia; Herrero, Marí­a José; Gondra, Leire; García-Pérez, Nélida; Garcia-Ledesma, P.; Martín-Penagos, Luis; Dall'Anese, Cecilia; Ariceta, Gema; Castaño, Luís; Madariaga, Leire

doi:10.1007/s00467-021-05066-z

Cited by 11 publications

(11 citation statements)

References 37 publications

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“…In participants from the Overall Cohort, SLC4A1 -rs116844389A was associated with ESKD, but not with serum variables. Renal complications of dRTA include nephrocalcinosis, nephrolithiasis, medullary cysts, and impaired kidney function, and it is common to develop moderate to severe CKD over time [ 137 , 138 ]. WDR72 -rs77593734T (OR:1.102; P = 1.4E-11; R2 = 0.251 with rs72747347) and rs690428A (OR:1.078; P = 1.5E-5; R2 = 0.279 with rs72747347) variants were recently identified to increase rapid eGFR Crea decline in a GWAS meta-analysis including 42 studies [ 139 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic variants affecting mitochondrial function provide further insights for kidney disease

Cañadas-Garre,

Baños-Jaime,

Maqueda

et al. 2024

BMC Genomics

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Background Chronic kidney disease (CKD) is a complex disorder that has become a high prevalence global health problem, with diabetes being its predominant pathophysiologic driver. Autosomal genetic variation only explains some of the predisposition to kidney disease. Variations in the mitochondrial genome (mtDNA) and nuclear-encoded mitochondrial genes (NEMG) are implicated in susceptibility to kidney disease and CKD progression, but they have not been thoroughly explored. Our aim was to investigate the association of variation in both mtDNA and NEMG with CKD (and related traits), with a particular focus on diabetes. Methods We used the UK Biobank (UKB) and UK-ROI, an independent collection of individuals with type 1 diabetes mellitus (T1DM) patients. Results Fourteen mitochondrial variants were associated with estimated glomerular filtration rate (eGFR) in UKB. Mitochondrial variants and haplogroups U, H and J were associated with eGFR and serum variables. Mitochondrial haplogroup H was associated with all the serum variables regardless of the presence of diabetes. Mitochondrial haplogroup X was associated with end-stage kidney disease (ESKD) in UKB. We confirmed the influence of several known NEMG on kidney disease and function and found novel associations for SLC39A13, CFL1, ACP2 or ATP5G1 with serum variables and kidney damage, and for SLC4A1, NUP210 and MYH14 with ESKD. The G allele of TBC1D32-rs113987180 was associated with higher risk of ESKD in patients with diabetes (OR:9.879; CI95%:4.440–21.980; P = 2.0E-08). In UK-ROI, AGXT2-rs71615838 and SURF1-rs183853102 were associated with diabetic nephropathies, and TFB1M-rs869120 with eGFR. Conclusions We identified novel variants both in mtDNA and NEMG which may explain some of the missing heritability for CKD and kidney phenotypes. We confirmed the role of MT-ND5 and mitochondrial haplogroup H on renal disease (serum variables), and identified the MT-ND5-rs41535848G variant, along with mitochondrial haplogroup X, associated with higher risk of ESKD. Despite most of the associations were independent of diabetes, we also showed potential roles for NEMG in T1DM.

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Section: Discussionmentioning

confidence: 99%

Genetic variants affecting mitochondrial function provide further insights for kidney disease

Cañadas-Garre,

Baños-Jaime,

Maqueda

et al. 2024

BMC Genomics

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“…In the kidney, CLCN5 encodes a chloride channel Cl-/H+ exchanger ClC-5, which played an important role in preventing protein loss, and this effect was weakened in patients with Dent disease who carried the defective CLC-5 [21]. Moreover, it was reported that primary distal renal tubular acidosis was a genetic disease caused by the mutation in ATP6V0A4 and ATP6V1B1, which can encode transporters that regulate acid-base balance in collecting tubes [22,23]. In addition, LAMA2 was reported to be a biomarker for MSK and can be used for early diagnosis of this disorder [24].…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Gene Expression Analysis in Patients with Medullary Sponge Kidney and a Retrospective Study

Lin

et al. 2022

BioMed Research International

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Objective. To establish better diagnosis thinking and provide advanced understanding of MSK, the CT imaging features, clinical characteristics, and the expression of suspected genes in the kidney spatiotemporal immune zonation and fetal renal development were investigated. Methods. 17 patients with MSK hospitalized in our hospital were selected as our research subjects. Human Phenotype Ontology, MalaCards: The Human Disease Database, GeneCards: The Human Gene Database, Human Protein Atlas, and Single Cell Expression Atlas were used to analyze this disease. Results. In our 17 patients, the incidence of MSK tended to be the same in male and female, and the onset age of MSK was probably 31-50 years old. The top one related disease of MSK was nephrocalcinosis and the most frequent phenotype related to MSK was nephrolithiasis. In addition, the expression of HNF1B, CLCN5, GDNF, ATP6V0A4, ATP6V1B1, LAMA2, RET, ACAN, and ABCC8 has been implicated in both human kidney immune zonation and fetal kidney development. Conclusions. HNF1B, CLCN5, GDNF, ATP6V0A4, ATP6V1B1, LAMA2, RET, ACAN, and ABCC8 could be independent indicators for the diagnosis and preventive intervention of MSK patients, and abnormal kidney development due to mutations in key genes was the underlying cause of MSK.

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“…This could be co-ordinated by a number of genes working together. For instance, SLC4A1 a causal gene for distal renal tubular acidosis or RBC abnormalities [ 64 ] and CKD has recently been identified in 30–80% of primary dRTA patients [ 65 ]. Furthermore, the SCLC4A1 gene may be a target for RCC therapy [ 66 ], as well as SLC4A1 was found to be strongly linked to blood pressure variations [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

System biology approaches identified novel biomarkers and their signaling pathways involved in renal cell carcinoma with different human diseases

Hossen

Samad²,

Ahammad

et al. 2022

Bioscience Reports

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Renal cell carcinoma (RCC) is a type of cancer that develops in the renal epithelium of the kidney. It is responsible for approximately 3% of adult malignancies, and 90-95% of neoplasms originate from the kidney. Advances in tumor diagnosis, innovative immune therapeutics, and checkpoint inhibitors-based treatment options improved the survival rate of patients with RCC accompanied by different risk factors. RCC Patients with diabetes, hepatitis C virus (HCV), or obesity (OB) may have a comorbidity, and finding the risk factor for better clinical treatment is an urgent issue. Therefore, the study focused on network-based gene expression analysis approaches to learning the impact of RCC on other comorbidities associated with the disease. The study found critical genetic factors and signal transduction pathways that share pathophysiology and commonly use dysregulated genes of the illness. Initially, the study identified 385 upregulated genes and 338 down-regulated genes involved with RCC. OB, chronic kidney disease (CKD), type 2 diabetes (T2D), and HCV significantly shared 28, 14, 5, and 3 genes, respectively. RCC shared one downregulated gene versican (VCAN) with OB and HCV and one downregulated gene oxidase homolog 2 (LOXL2) with OB and CKD. Interestingly, most of the shared pathways were linked with metabolism. The study also identified six prospective biomarkers, signaling pathways, and numerous critical regulatory and associated drug candidates for the disease. We believe that the discovery will help explain these diseases' complicated interplay and aid in developing novel therapeutic targets and drug candidates.

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Molecular aspects and long-term outcome of patients with primary distal renal tubular acidosis

Cited by 11 publications

References 37 publications

Genetic variants affecting mitochondrial function provide further insights for kidney disease

Genetic variants affecting mitochondrial function provide further insights for kidney disease

Single-Cell Gene Expression Analysis in Patients with Medullary Sponge Kidney and a Retrospective Study

System biology approaches identified novel biomarkers and their signaling pathways involved in renal cell carcinoma with different human diseases

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