Dataset Information

Uromodulin and progression of IgA nephropathy.

ABSTRACT:

Background

This study investigates the link between genetic variants associated with kidney function and immunoglobulin A (IgA) nephropathy (IgAN) progression.

Methods

We recruited 961 biopsy-proven IgAN patients and 651 non-IgAN end-stage renal disease (ESRD) patients from Ruijin Hospital. Clinical and renal pathological data were collected. The primary outcome was the time to ESRD. A healthy population was defined as estimated glomerular filtration rate >60 mL/min/1.73 m² without albuminuria or hematuria. Fifteen single-nucleotide polymorphisms (SNPs) were selected from a genome-wide association study of kidney function and genotyped by the SNaPshot. Immunohistochemistry in renal tissue and ELISA in urine samples were performed to explore the potential functions of genetic variations.

Results

The rs77924615-G was independently associated with an increased risk for ESRD in IgAN patients after adjustments for clinical and pathologic indices, and treatment (adjusted hazard ratio 2.10; 95% confidence interval 1.14-3.88). No significant differences in ESRD-free survival time were found among different genotypes in non-IgAN ESRD patients (log-rank, P = .480). Moreover, rs77924615 exhibited allele-specific enhancer activity by dual-luciferase reporter assay. Accordingly, the urinary uromodulin-creatinine ratio (uUCR) was significantly higher in healthy individuals with rs77924615 AG or GG than in individuals with AA. Furthermore, uromodulin expression in tubular epithelial cells was higher in patients with rs77924615 AG or GG. Finally, we confirmed that an increased uUCR (P = .009) was associated with faster IgAN progression.

Conclusion

The SNP rs77924615, which modulates the enhancer activity of the UMOD gene, is associated with renal function deterioration in IgAN patients by increasing uromodulin levels in both the renal tubular epithelium and urine.

SUBMITTER: Chen Z

PROVIDER: S-EPMC11322676 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

Uromodulin and progression of IgA nephropathy.

Chen Zijin Z Xu Lin-Lin LL Du Wen W Ouyang Yan Y Gu Xiangchen X Fang Zhengying Z Yu Xialian X Li Junru J Xie Lin L Jin Yuanmeng Y Ma Jun J Wang Zhaohui Z Pan Xiaoxia X Zhang Wen W Ren Hong H Wang Weiming W Chen Xiaonong X Zhou Xu-Jie XJ Zhang Hong H Chen Nan N Xie Jingyuan J

Clinical kidney journal 20240715 8

<h4>Background</h4>This study investigates the link between genetic variants associated with kidney function and immunoglobulin A (IgA) nephropathy (IgAN) progression.<h4>Methods</h4>We recruited 961 biopsy-proven IgAN patients and 651 non-IgAN end-stage renal disease (ESRD) patients from Ruijin Hospital. Clinical and renal pathological data were collected. The primary outcome was the time to ESRD. A healthy population was defined as estimated glomerular filtration rate >60 mL/min/1.73 m<sup>2</ ...[more]

PMID: 39145144

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Project description:BackgroundThis retrospective study aimed to evaluate the significance of serum immunoglobulin A/complement 3 (IgA/C3) ratio and glomerular C3 staining at the onset of disease for predicting progression of IgA nephropathy in children.MethodsA total of 41 children with IgA nephropathy were allocated to two groups according to proteinuria (proteinuria <50 mg/kg/day group and proteinuria ≥50 mg/kg/day group) to compare their clinical data. Receiver operating characteristic (ROC) curves were used to evaluate the optimal cutoff value of serum IgA/C3 ratio in two groups. According to the optimal cutoff value of serum IgA/C3 ratio and glomerular C3 staining, the children were divided into four groups: Group A (serum IgA/C3 ratio <2.025 and glomerular C3 staining <2.0); Group B (serum IgA/C3 ratio ≥2.025 and glomerular C3 staining <2.0); Group C (serum IgA/C3 ratio <2.025 and glomerular C3 staining ≥2.0); and Group D (serum IgA/C3 ratio ≥2.025 and glomerular C3 staining ≥2.0). Then, the risk factors [including proteinuria and glomerular filtration rate (GFR) and pathological findings] were compared in these 4 groups at onset of IgA nephropathy.ResultsSerum IgA/C3 ratio in the proteinuria <50 mg/kg/day group was significantly higher compared to the proteinuria ≥50 mg/kg/day group (P<0.01). According to ROC curves, the optimal cutoff value for the IgA/C3 ratio was 2.025 in two groups. At onset of IgA nephropathy, patients with IgA/C3 ratio <2.025 were predicted with nephrotic range proteinuria. When glomerular C3 staining was at the same level (glomerular C3 staining <2.0), GFR was significantly lower in group B (serum IgA/C3 ratio ≥2.025) compared with group A (serum IgA/C3 ratio <2.025). When serum IgA/C3 ratio was at the same level (serum IgA/C3 ratio <2.025), GFR was significantly lower in group C (glomerular C3 staining ≥2.0) compared with group A (glomerular C3 staining <2.0). Pathological findings and MEST (Oxford classification of IgA nephropathy) scores did not differ among the 4 groups at onset of the disease.ConclusionsSerum IgA/C3 ratio and glomerular C3 staining may be useful markers of the progression of IgA nephropathy in children, but not good markers for pathological findings at the onset of disease.

Dataset Information

Uromodulin and progression of IgA nephropathy.

Background

Methods

Results

Conclusion

Publications

Uromodulin and progression of IgA nephropathy.

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