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.

Figure 1

Survival receiver operating characteristic (ROC) curves for 1-, 3-, and 3-year survival. The areas under the receiver operating characteristics curves (AUCs) were 0.63, 0.70, and 0.61 for 1-, 2-, and 3-year follow-up, respectively. The cut-off values were 105.50 for 1-year follow-up and 105.40 for 2- and 3- ear follow-up.

Figure 2

Kaplan-Meier renal survival curves for patients with IgA nephropathy (IgAN) according to serum chloride levels. Patients with IgAN were classified into two groups according to serum chloride levels: a low chloride group (<105.4 mmol/L, red line) and a high chloride group (≥105.4 mmol/L, blue line). Log-rank rest revealed that the cumulative renal survival rates in the high chloride group were significantly worse than those in the low chloride group (p < 0.001).

Figure 3

A nomogram predicting the probabilities of 1-, 2-, and 3-year renal survival. We built a nomogram based on the prognostic model (including sCr, hypertension, T, Hb, and serum chloride (<105.40 mmol/L or ≥105.40 mmol/L)). Higher total scores based on the sum of the assigned number of points for each factor in the nomogram were associated with a worse prognosis.

Figure 4

c-indices and calibration curves for the new model. 200 sample bootstrapped calibration plots for the prediction of 1–3-year renal survival are shown. The gray line represents the ideal fit while the black line represents practical fit. The c-indices for 1-3 years were 0.80 (95% CI: 0.65-0.94), 0.86 (95% CI: 0.77-0.94). and 0.78 (95% CI: 0.55-0.97), respectively. Brier scores were 0.06 (95% CI: 0.04-0.09), 0.09 (95% CI: 0.05-0.13). and 0.16 (95% CI: 0.06-0.32), respectively.