Association between Immunoglobulin M and Steroid Resistance in Children with Nephrotic Syndrome: A Retrospective Multicenter Study in Japan

Abstract

Background: The prognosis of steroid resistant nephrotic syndrome (SRNS) in children is poorer than steroid-sensitive cases. The diagnosis is made following the response to the initial 4-week corticosteroid therapy, which might be accompanied by side effects. However, predictive indicators at initial diagnosis remain unknown. We aimed to investigate whether selectivity index (SI) and other indicators at initial diagnosis, for example, serum immunoglobulin M (IgM) and total serum protein albumin ratio (TA ratio, total serum protein level over albumin level), can predict SRNS. Methods: Eighty children were enrolled from seven hospitals in Japan between January 2008 and December 2019 (mean age 4.7; male 65.0 %). Of the enrolled 80 children, 13 (16.3 %, M:F = 5:8) had been diagnosed as steroid-resistant after the initial treatment with steroids. The association between serum IgM (tertile categories; low: 24-133; middle: 134-169; and high: 169.1-510 mg/dl), SI (<0.2 or ≥0.2), and TA ratio (tertile categories; low: 1.8-2.6; middle: 2.62-3.75; and high: 3.8-15.3) at initial diagnosis and steroid resistance was evaluated with logistic regression adjusting for age and sex. Results: Low levels of serum IgM were significantly associated with steroid resistance (adjusted odds ratio (aOR) = 6.94; 95% confidence interval (CI): 1.12-43.11). TA ratio and SI were not significantly associated with steroid resistance. Conclusions: Low levels of serum IgM at initial diagnosis might predict steroid resistance among Japanese children with idiopathic nephrotic syndrome.

Assessment of Immunoglobulin M in Children with Steroid Resistant Nephrotic Syndrome

“…Median age in the SRNS group was 10 years and in the SSNS group was 12.5 years with a minimum age of almost the same in both groups Also, Mortazavi and Khiavi (11) showed that there is no statistically difference between steroid resistant and steroid sensitive nephrotic children regarding to sex and age. In contrast Udagawa et al (2) showed that among 80 patients with idiopathic nephrotic syndrome, 13 patients (M:F = 5:8) with mean age 3.87 ± 3.27 were steroid-resistant and 67 patients (M:F = 47:20) were steroid-sensitive with mean age = 4.88 ± 3.98 years, with a statistical difference between steroid resistant and steroid sensitive nephrotic children regarding to sex and age (p< 0.05).…”

“…Steroid resistance is often diagnosed as a failure to induce complete remission after 4 weeks of standard steroid therapy with 60 mg/m 2 intravenous or oral prednisolone per day. In accordance with the guidelines of the International Study of Kidney Disease in Children, complete remission is defined as a reduction in proteinuria to < 0.2 mg/mg protein-creatinine ratio in the first-morning urine void, or negative dipstick test results for three consecutive days (2) .…”

“…There was a significant higher percent of albuminuria (++) and higher 24 hours protein in urine of steroid resistant nephrotic group compared to steroid sensitive nephrotic group (Table 4). (2) . Colucci et al (6) demonstrated that atypical IgM on the surface of T cells predisposed patients to the onset of severe childhood idiopathic nephrotic syndrome.…”

“…Idiopathic nephrotic syndrome (INS) is divided into steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) taking in account that response to steroid therapies is highly correlated with tissue subtype and disease progression prognosis, the International Study of Kidney Disease in Children (ISKDC), revealed that the great portion of children with INS had minimal change nephrotic syndrome (MCNS) in their renal biopsies (2) .…”

“…According to the International Study of Kidney Disease in Children (ISKDC), SRNS is defined as a non-response to an 8-week exposure (at a minimum) of 60 mg/m 2 prednisone per day, or 2 mg/kg prednisone per day for 4 weeks followed by 40 mg/m 2 per day on alternate days for 4 weeks (2) .…”