Clinical characteristics of IgA nephropathy associated with low complement 4 levels

Abstract

Objective: C4 deficiency is the most commonly inherited immune disorder in human. The present study investigated the characteristics of the IgAN patients with low serum C4 levels.Methods: We performed a prospective observational study. Clinical as well as histopathologic parameters were assessed. A Kaplan-Meier survival analysis was performed concerning the primary outcome defined as the serum creatinine increased 1.5-fold from baseline. The prognostic significances of clinical and histopathologic parameters were determined using Cox proportional hazards models. Results: Five-hundred twelve biopsy proven IgAN cases were available for analysis with a median follow-up of 38.4 months. Ninety-nine cases (19.34%) presented with low C4 levels (LowC4 group) and the other 413 cases did not (NlowC4 group). At the time of renal biopsy, renal injury was lighter in the LowC4 group compared with the NlowC4 group. Renal C4 deposition was significantly decreased while IgM deposition was increased in the LowC4 group. A correlation analysis shows that lower C4 levels were associated with better renal presentations at biopsy. However, the risk of developing the primary outcome was significantly greater in those with low C4 levels. Specifically, during the follow-up period, the risk of developing primary outcome was nearly ten folds higher in those with low C4, compared to those without low C4. Conclusion: There is a high prevalence of low C4 levels in IgAN patients. These patients with low C4 levels exhibited better renal presentations at the time of renal biopsy, whereas might be associated with a poor prognosis.

Glomerular C4 deposition and glomerulosclerosis predict worse renal outcomes in Chinese patients with IgA nephropathy

“…In contrast, Zhu et al found that serum C4 level was positively associated with MAP, proteinuria, serum IgA, serum C3, and STscores, whereas it was negatively correlated with eGFR, serum IgM, IgG, IgM, and C3 deposition. The report of Zhu et al indicated that patients with a low C4 level exhibited less severe renal injury and might have poor outcome [18]. Consistent with a previous study by Min et al [20], we found that a decreased C3/C4 ratio was associated with poor renal outcomes.…”

“…IgAN is recognized as a highly variable course ranging from a benign condition to progression to ESRD. Although previous studies have identified multiple risk factors influencing IgAN progression, including male, hypertension, renal impairment, urinary protein excretion over 1 g/d, and severe pathology [16,17], increasingly researchers are focusing on the role of complement [11,18]. However, the predictive value of serum complement level and complement deposition in prognosis of IgAN is still controversial.…”

Increased C4 and decreased C3 levels are associated with a poor prognosis in patients with immunoglobulin A nephropathy: a retrospective study

“…Although serum levels of C3 and C4 frequently fluctuate within the normal range in IgAN patients, studies have increasingly focused on the role of complement in the pathogenesis of IgAN [14–17]. However, the relationship between serum complement levels and the renal prognosis of patients with IgAN remains controversial.…”

“…Lbels et al found an independent association between serum C4 levels and patient outcomes, suggesting that these parameters reflect the severity of chronic inflammation [19]. Furthermore, Zhu et al found that higher C4 levels at the time of renal biopsy were associated with a greater degree of renal injury, including lower eGFR, higher MAP and 24-h urinary protein, and more severe pathological features, and lower C4 levels were related to poor prognosis, a counter-intuitive finding [14]. These studies are all limited in a variety of ways as the authors considered either C3 or C4 alone but not in combination, and this approach may therefore be inadequate for discerning the association between complement levels and renal outcomes.…”

Study of correlation between polymorphism of ST6GALNAC2 and susceptibility to IgA nephropathy

“…The serum IgA levels of the majority of patients with IgAN increase (14). However, due to lack of specificity, this cannot be regarded as a criterion for assisting clinical diagnosis.…”