To the best of our knowledge, this study is the first to compare eGFR between AQP4 antibody-positive NOMSD and MS patients. In this study, we found a slight reduction of eGFR (especially eGFRCysC) in NMOSD patients, compared to MS patients and HCs, although the average eGFR were within the normal range in all groups.
eGFR is a universal marker of renal function[9], and decreased GFR represents the presence of glomerular small vessel disease [19]. The estimation of renal function using serum CysC levels has clinical advantages as it is not influenced by the blood concentrations, muscle mass, gender, or age [20, 21]. Therefore, to a certain degree, eGFRCysC may be superior to eGFRCr for evaluating renal function in NMOSD. However, studies have showed that glucocorticoid administration was associated in a dose-dependent fashion with increased CysC values, leading to a dose-dependent underestimation of GFR calculations based on CysC[22]. Thus, steroid-free status may improve the accuracy of the CysC-based equations. In order to reduce potential bias of results caused by glucocorticoids treatment, we analyzed the serum CysC data from NMOSD patients who had never received steroids or other disease-modifying immunosuppressive therapy at least three months prior to the admission.
The AQP-4 is expressed in principal cells of collecting duct of kidney, where about 15% of tubular fluid was reabsorbed through AQP-2, AQP-3 and AQP-4. Both AQP-4 and AQP-3 are located in the basolateral membrane of principal and responsible for the transportation of water, which is reabsorbed by AQP-2 from tubular fluid into intercellular fluid[23]. If either AQP-4 or AQP-3 was dysfunction, the other one might compensate to keep osmotic pressure in tubular fluid in some degree. And these theories are confirmed by Chou CL et.al, who has reported the mild defect in urinary concentrating ability in AQP-4 knockout mice[5]. Furthermore, it was also discovered that NMOSD patients show a urinary concentrating defect[6]. Thus, the deposition of AQP4-IgG and the loss of AQP4 may potentially lead to damage in kidney. In our study, we found that the mildly lower eGFR was found in NMOSD, but still in the normal range. This phenomenon may be cause by the fact that AQP-4 might play a major role in concentration and dilution of renal tubules, but not in glomerular filtration. Besides, there are so many factors affecting GFR in complex ways, which needs further development.
In a recent study, higher CysC concentration was observed in renal transplant recipients on low-dose prednisone treatment (5–10 mg/d) compared to those on steroid-free immunosuppression [24]. Interestingly, in our study, we did not find higher CysC concentrations in acute-phase NMOSD patients with low-dose glucocorticoid therapy before acute attack, compared to acute-phase NMOSD patients without glucocorticoid therapy before acute attack. The greater increase of CysC in stable-phase NMOSD with glucocorticoid therapy may be explained by a result of the decrease in the inflammatory process. Besides, 27.56% of stable-phase NMOSD patients with low-dose glucocorticoid therapy had eGFRCysC< 90 ml/min/1.73 m2, which implies a substantial loss of glomeruli and impaired renal reserve. In addition, no changes of renal function occurred in MS patients in this study, which was contrary to a previously reported result[25] on progressive type MS. The difference in renal function may be due to the different subtypes of MS. The enrolled MS patients in this study were relapsing-remitting MS, while the previous study was chronic (both primary and secondary) progressive MS patients.
Several limitations need to be addressed in our study. In the present study, we detected differences in eGFR, but results of all groups are in the normal range. However, these still indicated that reduced renal function has occurred in patients with AQP4 antibody-positive NMOSD compared to MS patients and HCs, suggesting that more attention should be paid to protect the renal function throughout the disease stage, especially when applying nephrotoxic drugs. Additionally, the number of patients was relatively small and blood samples were just obtained once. However, to the best of our knowledge, this is the first study to investigate renal function in NMOSD patients. Our hospital is the major research unit focused on this condition in China. More cases will be collected and blood samples will be obtained at different time points for the future investigation. Furthermore, additional measurement of proteinuria and BMI may improve the sensitivity and specificity of our assessment of renal function, which can be investigated in the future.