Dataset Information

Elevated Serum Chloride Levels Contribute to a Poor Prognosis in Patients with IgA Nephropathy.

ABSTRACT:

Introduction

The identification of reliable prognostic factors is a crucial requirement for patients with IgA nephropathy (IgAN). Here, we explored the relationship between serum chloride levels and prognosis in patients with IgAN.

Methods

We recruited all patients with primary IgAN, as diagnosed by renal biopsy, between 1^st January 2015 and 1^st April 2019. Patients were divided two groups (high chloride group and low chloride group) based on the best cut-off values from survival receiver operating characteristic (ROC) curves. The baseline clinicopathological characteristics of two groups were then compared. Cox proportional hazard models were used to determine the prognostic value of serum chloride levels in patients with IgAN. Finally, we screened reliable prognostic indicators and built a clinical prediction model and validated the performance of the model.

Results

Compared with patients in the high chloride group, patients in the low chloride group had significantly lower levels of 24-hour urinary total protein (24 h-UTP), serum creatinine (sCr), and higher levels of hemoglobin (Hb), albumin (all p < 0.05), and less proportion of Oxford classification grade E1 (endothelial cell proliferation) and T2 (renal tubule atrophy or renal interstitial fibrosis). Cox analysis revealed that serum chloride level ≥ 105.4 mmol/L was a significant and independent risk factor for prognosis in patients with IgAN (p < 0.05). Serum chloride, sCr, T, hypertension, and Hb were used to generate a predictive model for prognosis. Thec-indices of our predictive model were 0.80, 0.86, and 0.78, for 1, 2, and 3 years, respectively; Brier scores were 0.06, 0.09, and 0.16, respectively.

Conclusions

A serum chloride level ≥ 105.4 mmol/l was identified as a significant and independent risk factor for the prognosis of patients with IgAN. A predictive prognosis model was generated using serum chloride, sCr, T, hypertension, and Hb; this model exhibited a good predictive effect.

SUBMITTER: Zhai Y

PROVIDER: S-EPMC8739901 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIt has been suggested that mesangial IgA deposits are dimeric or polymeric in IgA nephropathy (IgAN). However, evidence concerning the molecular form of serum IgA in IgAN is controversial. And there is no direct evidence that the serum levels of joining chain- (J chain-) containing IgA (J-IgA) are elevated in IgAN. In this study, we aimed to measure serum J-IgA and glomerular J chain deposition with anti-J chain monoclonal antibody in IgAN.MethodsBALB/c mice were immunized with human J chain-GST recombinant peptide to obtain anti-J chain monoclonal antibody. The levels of serum total IgA and J-IgA were measured by sandwich enzyme-linked immunosorbent assay in 115 patients with IgAN and 117 healthy volunteers. J chain deposition in kidney specimens was analyzed by immunohistochemistry staining.ResultsSerum levels of total IgA1 were elevated in IgAN patients compared to healthy subjects. However, serum levels of IgA, J-IgA, and J chain-containing IgA1 (J-IgA1), the J-IgA to total IgA ratio, and the J-IgA1 to total IgA1 ratio were not significantly different between IgAN patients and healthy subjects. Western blot analysis and gel filtration analysis using purified IgA1 also showed that the proportion of J chain-containing polymeric IgA1 was lower in IgAN patients compared to healthy subjects. No correlation was found between serum J-IgA or J-IgA1 and clinical features in IgAN. Immunohistochemistry analysis showed that glomerular J chain was positive in 12 IgAN patients (57.1%). The values of the J-IgA to IgA ratio and J-IgA1 to IgA ratio were significantly higher in IgAN patients with glomerular J chain deposition than those without. However, the serum levels of J-IgA and J-IgA1 and the J-IgA1 to IgA1 ratio were not significantly higher in two subgroups.ConclusionsAlthough serum levels of total IgA1 were elevated in IgAN, the serum levels of J-IgA1 were not elevated. And serum J-IgA, serum J-IgA1, and J chain deposition were not correlated with disease severity in IgAN.