Several pediatric studies examined the clinical symptoms, steroid response, relapses, and renal outcomes in idiopathic nephrotic syndrome children with or without IgM mesangial deposition. We, for the first time, investigated the predictive value of IgM mesangial deposition on patient outcomes in newly-diagnosed MCD adults. In our adult-onset MCD cohort, the multivariate linear regression analysis revealed that IgM deposit positivity is independently associated with a significantly higher frequency of relapses. Besides, further subgroup analysis showed that patients who developed MCD at the age of > 40 years old were associated with a higher frequency of relapses than those < 40 years old.
Previous studies showed a significantly higher mean serum IgM level in children with positive IgM deposition [14, 15]. In our study, there is a trend of increased IgM and IgM/IgG ratio in the positive IgM group but did not achieve the statistical significance, probably due to the small sample size. Previous studies showed the IgM deposition increased risks of chronic kidney disease (CKD) and end-stage kidney disease in children for more than ten years of follow-up [2, 5], showing the clinical implication of IgM positivity in MCD. Our study did not examine renal failure because of the reserved eGFR and the relatively short follow-up period in our cohort, but further research of IgM positivity on long-term renal outcomes in adult-onset MCD is warranted.
On the other hand, In our study, the frequency of relapses is more common in men with IgM deposition by our subgroup analysis. In an MCD study composed of both children and adults, gender is not a determinant of renal function progression . Nevertheless, it has been reported that the renal function of males declined more rapidly than females in nondiabetic CKD .
In previous studies, children with IgM deposition were more likely to have hypertension [2, 17] and hematuria [5, 17]. There was no difference in blood pressure, lipid profile, renal function, hematuria, and proteinuria in MCD with or without IgM deposition [1, 6, 18], which were also noted in our study. Besides, according to our subgroup analysis, a higher frequency of relapses is more common in patients with lower eGFR < 97.8 mL/min/1.73 m2, serum albumin < 2.5 g/dL group, serum cholesterol ≧ 405 mg/dL, the presence of nephrotic-range proteinuria, and the absence of microscopic hematuria. In accordance with our study, a previous study also demonstrated that microscopic hematuria is a favorable sign .
There are no randomized controlled trials on the treatment of MCD with IgM deposition. Corticosteroids constitute the mainstay of therapy in MCD. The prevalence of steroid resistance in idiopathic nephrotic syndrome patients with positive IgM deposition is inconclusive, varying from 0 to 52% . Several studies showed a higher steroid dependence in MCD children with IgM deposition [2, 9]. Conversely, IgM deposition was not related to increased steroid resistance and steroid dependence in other pediatric studies [1, 17]. In our adult MCD cohort, there was also no difference between steroid resistance between patients with or without IgM deposition. Furthermore, in terms of time to partial remission, time to complete remission, and time to the first relapse after treatment, there was no difference between these two groups.
Adjuvant immunosuppressive therapy includes CsA, CYC, MPA, and levamisole, etc. . Several studies evaluated the effect of adjuvant immunosuppressive therapy in idiopathic nephrotic syndrome [22–24]. CsA and CYC significantly reduced relapse risk compared with prednisolone alone in the frequent relapsing idiopathic nephrotic syndrome in pediatric patients . In a study of idiopathic nephrotic syndrome, CsA and CYC are both effective and well-tolerated in adults and children . CYC has more side effects, such as bone marrow suppression, gonadal toxicity, infection, seizure, malignancies, etc. . Therefore, a study showed the CsA potentially indicated as first-line therapy in steroid-resistant nephrotic syndrome . The patients with positive IgM deposition have a better response to CsA than CYC . Combined CsA and prednisolone can be more effective than prednisolone alone in MCD children with positive IgM deposition . No significant difference in response to non-corticosteroid treatment was found between the MCD patients with or without IgM positivity [1, 2, 17, 27]. Our sample size is too small to evaluate the effect of adjuvant immunosuppressive therapy.
There are some limitations in the present study. First, the sample size is small, so we cannot evaluate the subgroup analysis optimally. Second, there is a relatively short follow-up period, so we did not evaluate further renal function. Third, this is only a retrospective study, and the decision on dosages and types of immunosuppressive agents was at the discretion of each attending nephrologist. However, the average dosages of immunosuppressive agents are similar between patients with and without IgM mesangial deposition, as shown in Supplementary Table 1.
In conclusion, our novel findings indicated that newly diagnosed MCD adults with IgM mesangial deposition are more likely to experience disease relapses than those without, particularly in patients with older age, male, hypoalbuminemia, lower eGFR, the presence of nephrotic-range proteinuria, or the absence of microscopic hematuria. Therefore, immunosuppressive agents may be tapered slowly with close follow-up in these patients. Besides, MCD adults with a positive IgM deposition might be benefited from combined immunosuppressive therapy than prednisolone alone, as suggested in previous pediatric studies [22, 23, 26].