Our study showed that there were some clinicopathological changes of PNS in children over 10 years (2006–2015). Children with PNS accounted for 34.57% of all hospitalized children in the Department of Pediatric Nephrology Rheumatology over the 10-year period. In 1982, children with PNS in some provinces and cities in China accounted for 21% of all hospitalized children and this rate was 31% in 1992[12]. This finding suggests that hospitalization for PNS had increased over these years. In this study, the group B was twice the size of group A, which may have been a result from the economic development and convenient public transportation. In our study, the ratio of boys to girls with PNS was 3:1 and the subjects were mainly pre-school children, which was consistent with domestic and international studies[12][13]. Because of disease relapse or infused cyclophosphamide, the number of hospitalizations fluctuated between 1 and 17 times, and 59 patients in Group A still needed to be admitted to hospital in the period of Group B. The days of hospitalization varied from 1 to 65 days with a mean length of 10.41 ± 8.83 days. This hospital stay was longer than the mean length of stay in Gipson DS’ study (5 ± 0.1 days)[8].
In our study, there was no significant difference in the response to glucocorticoids between the two groups. Dincel et al[14] found that 88.3% of children with PNS were SSNS and 11.7% of patients were SRNS, which was in accordance with our findings. Another study showed that approximately 10% of patients with PNS had SRNS, and SRNS pathology was predominantly FSGS[13]. Even though our study did not show any difference in the rate of SRNS, the proportion of SRNS was higher than that in Dincel et al’s study[14], and slightly higher than that (10–20%) previously reported in China[11]. This suggested an increasing trend of SRNS in recent years. There were 48 patients with an unknown steroid response because we were unable to follow them up.
MCD, MsPGN, and FSGS are the most common pathological types of PNS in children[14][15][1]. Our findings further supported this conclusion. In our study, the rate of MsPGN gradually decreased in recent years, while that of MN increased. The specific etiology of this finding is unclear. One reason for the decrease in the percentage of MsPGN is due to the increasing tendency of MPGN or MN. In addition, a multicenter study in China[16] showed that an increased incidence of idiopathic membranous nephropathy (IMN) was associated with an increase in Particulate Matter 2.5(PM2.5) in the environment. How the mechanisms of exposure to PM2.5 increase the risk of MN remains to be elucidated. Furthermore, a previous study in our center[17] indicated that the incidence of children with FSGS and MN showed an upward trend in the past 20 years. Especially in the latest 5 years, the incidence of FSGS and MN in renal pathological types has significantly increased. However, other results[18] demonstrated that the main pathology of PNS in children was FSGS, which may have been related to hospitals receiving difficult referral cases. On the other hand, in our study, there were two children with FSGS and recurrent disease who had repeated renal biopsies, including one with pathological findings of MN (II–III), which progressed to MN (III) and FSGS. The other child showed a change from minimal changes to FSGS, and the pathological findings were more severe than the former ones. For those repeatedly refractory patients, repeated renal biopsy can assess the severity of disease, predict the outcome and adjust the treatment regimen timely.
In our study, 512 (47.76%) children with PNS had complications in hospital. In particular, the incidence of infections was significantly higher in group B than in group A. However, there were no significant differences in other types of complications between the groups. Some previous studies have shown that 60% of patients[19][8] have at least one complication, and14–16% of patients have at least one serious complication in the course of PNS. Historically, infections were the leading cause of mortality in children with PNS, and even now, infection is the leading cause of morbidity in children with PNS[20][2]. Infections are due to urinary loss of immunoglobulins and complement, impaired lymphocytic function. The reason for higher incidence of infection in group B in our finding was not clear, but it may be related to more air pollution. Song et al[21] have shown that the hospitalization rate of children with pneumonia was positively correlated with levels of the air pollution marker PM 2.5, and ambient PM 2.5 contributed as much as 33.1% (95% confidence interval: 22.6%, 42.4%) to total acute lower respiratory infection (< 5 years) deaths in China. Therefore, we speculated that the increase in hospitalization is due to the rising rate of infection.
Glucocorticoids are still the first-line regimen for children with PNS. However, for SRNS or FRNS, the option of immunosuppressants has changed over recent years. The proportion of CsA and Triptolide administrated was decreased, while the proportion of TAC used was increased in our study. The reasons for this finding were related with the recommendation of TAC in the treatment guidelines in China and some other countries. However, CsA and Triptolide have severe side effects. In addition, the administration of immunosuppressive drugs improves the remission rate of refractory PNS. A previous report[19] showed that 51% of patients with PNS received two or more immunosuppressive agents. For children with SRNS, Trautmann A et.al showed that using enhanced immunosuppressive agents had a good effect[13]. CTX was the most used immunosuppressant[22], and our study confirmed it. Several case series suggest that TAC is effective for FRNS or SDNS[2]. Moreover, TAC was superior to MMF in maintaining remission of SRNS[23]. Reports[24][25] found that Adalimumab and Rituximab can help patients to achieve a long-term remission period, improve quality of life, and reduce the hospitalization rate. However, Adalimumab and Rituximab are not widely used because of high costs. However, using immunosuppressive drugs also increased the rate of infection in children with PNS. Therefore, when using immunosuppressive agents, clinicians need to consider the advantages and disadvantages of these agents.
Our study also has some limitations. Primarily, this was a retrospective, single-center study. Future studies need to include other medical centers to identify changes in the clinicopathological features of PNS. In addition, the biopsy reports were not reported by the same pathologist because the study lasted 10 years.
In conclusion, our study showed the rate of complications has significantly increased with mainly infectious complications. The rate of MsPGN has decreased in recent years, while that of MN increased. Glucocorticoids are still the first-line treatment for children with PNS. However, due to the choice of immunosuppressive agents, the use of Tacrolimus in children increased whereas Tripterygium decreased. This study was a part of a series of studies which aim to further examine clinicopathological features and complications of children with PNS.