Kidney Dysfunction Identified as a Possible Risk Factor for Relapse and Poor Prognosis in NMOSD


Patients with aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorder exhibited higher urine pH compared to those with multiple sclerosis and healthy controls.

Using a retrospective cohort, findings revealed kidney dysfunction, including glomerular hyperfiltration and impaired urine concentrating ability in patients with aquaporin-4 (AQP4)-IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD) relative to those with multiple sclerosis (MS) and healthy controls (HCs). All told, kidney dysfunction may be a possible risk factor for relapse and poor clinical prognosis in AQP4-IgG-seropositive NMOSD.

Performed at the First Affiliated Hospital of Zhengzhou University, the study included 327 consecutive patients with AQP4-IgG-seropositive NMOSD, 313 patients with MS, and 526 HCs who underwent kidney function testing and routine urine examinations between 2016 and 2020. Of these, 135 with AQP4-IgG-seropositive NMOSD, 128 with MS, and 136 HCs completed the study. At baseline, the mean glomerular filtration rate (eGFR) was 128.6 mL/min (SD, 21.5), with most patients (41.5%) between 120 and 140 mL/min.

Led by senior investigator Xuejing Wang, a professor at the First Affiliated Hospital of Zhengzhou University, the study aimed to explore the association of eGFR with the incidence of relapse and clinical prognosis of NMOSD. Results indicated that eGFR was significantly higher in this patient population relative to those with MS (P <.001) and HCs (P <.001), respectively, while no difference between patients with MS and HCs (P >.05) was observed. Similarly, investigators observed significantly lower serum cystatin C, serum creatinine, serum urea, and urine specific gravity among AQP4-IgG-seropositive NMOSD vs MS (P <.001) and HCs (P <.001), respectively, while no significant differences were observed between those with MS and HCs.

Additional findings between the groups showed significantly higher urine pH in those with NMOSD vs MS and HC groups (P <.001). Notably, eGFR, urinary β2-microglobulin, and urine pH were positively correlated with Expanded Disability Status Scale (EDSS) scores (P <.05) and anti-AQP4 antibody titer (P <.05), respectively, while the serum creatinine, serum cystatin C, and serum urea were negatively associated with EDSS scores (P <.05) and anti-AQP4 antibody titer (P <.05), respectively. A subsequent analysis found no correlation between eGFR and AQP4 titers (n = 31; r = .034; P = .86).

Over a median follow-up of 3.1 years, results showed an increased rate of relapse in patients with NMOSD with increased eGFR. The association was observed between the risk of relapse and eGFR categories, with the highest relapse risk for those with eGFR greater than 160 mL/min. To further evaluate whether the relationship between eGFR and relative risk of the occurrence of relapse in patients with AQP4-IgG-seropositive NMOSD was linear, a restricted cubic spline model with 4 knots was fitted, and no evidence of non-linearity was found (p for non-linearity = 0.50) when eGFR was as a continuous variable and after adjusting for potential confounding factors.

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Poor prognosis, defined by an EDSS score of at least 4.5 at follow-up, was identified in 84 cases, with an overall poor clinical prognosis incidence rate of 51.9%. Univariate analyses using logistic regression models revealed that eGFR (OR, 4.013; 95% CI, 2.372-6.789), sex (OR, 8.667; 95% CI, 3.075-24.426), depression (OR, 25.038; 95% CI, 5.673-110.503) and initial EDSS score (OR, 0.102; 95% CI, 0.045-0.232) were significantly associated with clinical prognosis. After adjusting for all other variables, eGFR was found to still be an independent risk factor of poor prognosis.

There were a few noted limitations to the study, including the fact that kidney function changes with time, and that longer follow-up may contribute to misclassification bias. In addition, there was no information on lifestyle, body mass index, or muscle mass, although investigators included clinical diagnoses of comorbidities to exclude these factors.

"While we recognize that the sensitivity of these lifestyle-related diagnoses is low, they are highly specific and may adjust for some additional confounding," Wang et al wrote. "And we acknowledge the existence of residual and unknown confounding. In conclusion, our findings may help further gain new insight into the impact of AQP4-IgG on the peripheral organs. In addition, the determination of kidney function is easy, cost-less, and less invasive, and its values are stable."

1. Chen Y, Wang Y, Jin R, et al. Renal dysfunction in AQP4 NMOSD and MS; a potential predictor of relapse and prognosis. Clinical Immunol. 2024;259:109875. doi:10.1016/j.clim.2023.109875
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