Comparison of healthy controls and SLE patients
This study included 196 SLE patients and 52 HCs. Table 1 shows comparisons of the clinical variables between the SLE and HCs groups. All SLE patients and HCs were females and Mexican-Mestizo. SLE patients had a similar median age compared with HCs (45 vs 47 years, p=0.87). Body mass index (BMI) was not significantly different between the SLE and HCs groups (27.3 vs 27.9, p=0.86).
Characteristics of the SLE patients
Table 1 also includes a description of the selected characteristics of the total group of SLE patients. Of 196 SLE patients, 28.1% had positive anti-dsDNA antibodies. The median SLEDAI score was 2 points. Seventy-six (38.8%) SLE patients had active disease (SLEDAI>4). The r-SLEDAI ranged from 0 to 12 points. Forty-three SLE patients (21.9%) presented renal disease activity. All SLE patients were receiving glucocorticoids, although only 60 (30.6%) were receiving a dosage >10 mg/day. Of the total SLE patients, 74% were receiving immunosuppressive therapy.
Comparison of MIF and adipokine levels between SLE and HCs
Figure 1 presents the comparison of MIF and adipokine levels between the SLE and HCs groups. Serum MIF and adiponectin concentrations were higher in SLE patients than in HCs. Increased MIF levels were observed in SLE patients [9.1 (0.6-43.9) ng/mL vs. 5.3 (0.3-32.7) ng/mL, p=0.02]. Adiponectin concentrations were also higher in SLE patients than in HCs [14.5 (0.6-45.1) µg/mL vs 10.2 (1.6-24.3) µg/mL, p<0.001]. Resistin levels were lower in SLE patients than in HCs [9.1 (2.4-37.1) ng/mL vs 14.3 (1.3-55.9) ng/mL], p<0.001). No differences were identified in the concentrations of leptin between SLE patients and HCs [18.6 (1.6-136.5) ng/mL vs 18.3 (0.31-87.48) ng/mL, p=0.92].
Comparison of MIF and adipokine levels in HCs, renal SLE and non-renal SLE
Figure 2 shows the comparison of the MIF and adipokine levels among the HCs, renal SLE and non-renal SLE groups. The three groups had differences in adiponectin levels (p<0.001). Post hoc analysis showed that adiponectin concentrations were more elevated in renal SLE patients than in HCs [19.0 (7.3-45.1) µg/mL vs 10.2 (1.6-23.4) µg/mL, p<0.001] and non-renal SLE patients [19.0 (7.3-45.1) µg/mL vs 13.3 (0.6-37.0) µg/mL, p=0.002]. Non-renal SLE patients presented higher levels of adiponectin than HCs [13.3 (0.6-37.0) µg/mL vs 10.2 (1.6-23.4) µg/mL, p=0.002]. Resistin concentrations were more elevated in HCs than in non-renal SLE patients [14.3 (1.3-55.9) ng/mL vs 8.9 (2.5-37.1) ng/mL, p<0.001] and renal SLE patients [14.3 (1.3-55.9) ng/mL vs 10.7 (6.2-26.2) ng/mL, p<0.001]. MIF and leptin levels were not significantly different among the three groups.
Comparison of variables between renal SLE and non-renal SLE
Renal SLE patients received higher doses of prednisone than patients without renal activity [20 (2.5-75) mg/day vs 7.5 (2.5-50.0) mg/day, p<0.001], but the frequency of the concurrent use of immunosuppressive drugs was similar in renal SLE and non-renal SLE patients (p=0.64). Furthermore, renal SLE and non-renal SLE patients had similar disease durations [43 (18-62) years vs 46 (18-73) years, p=0.13]. Other comparisons of variables between renal SLE patients and non-renal SLE patients are described in Table 2.
Correlations of MIF and adipokines with clinical variables
Table 3 describes the correlations of MIF and adipokines with clinical and laboratory variables. Lower serum MIF levels were correlated with increased age (p=0.003) and longer duration of SLE (p=0.004). MIF did not correlate with SLEDAI, rSLEDAI, proteinuria or other features. Serum leptin levels correlated with BMI (p<0.001), proteinuria (p=0.01) and estimated glomerular filtration rate (eGFR) (p=0.02). High concentrations of adiponectin correlated with proteinuria (p=0.009), rSLEDAI (p=0.004), and high Mex-SLEDAI scores (p=0.03). However, adiponectin levels were negatively correlated with eGFR (p=0.05). Additionally, serum adiponectin levels correlated with glucocorticoid dose (p=0.02) and BMI (p<0.001). Correlations were observed between resistin levels and proteinuria (p<0.001), serum creatinine (p=0.02), SLICC/ACR (p=0.01), and glucocorticoid dose (p=0.03). No correlations were observed between serum leptin or resistin and proteinuria, SLEDAI or rSLEDAI.
Correlations of MIF and adipokines with parameters of renal activity in the 43 renal SLE patients
We investigated the correlations of MIF and adipokine levels with parameters of renal activity in renal SLE patients. MIF levels were significantly correlated with proteinuria in g/day (rs= -0.47; p=0.008) but not with serum creatinine (rs= -0.24; p=0.13), 24-hour creatinine clearance (rs= -0.14; p=0.40), or eGFR (rs= 0.15; p=0.33). Furthermore, in renal SLE patients, adiponectin levels correlated only with serum creatinine (rs= 0.34; p=0.03) but not with other parameters of renal activity. Resistin and leptin did not show any correlations with renal inflammatory features (data not shown).
Variables associated with the severity of proteinuria (g/day): Results of the multiple linear regression analysis
Table 4 demonstrates the findings of the factors associated with the severity of proteinuria in g/day obtained in the multiple linear regression analysis. With the enter method, the variables associated with the severity of proteinuria (g/day) were glucocorticoid dose (p<0.001), adiponectin level (p<0.001), MIF level (p=0.01) and age (p<0.001). Using the forward stepwise method in multivariable linear regression analysis, the factors associated with the severity of proteinuria in g/day were higher glucocorticoid doses (p<0.001), higher adiponectin levels (p=0.001), lower MIF levels (p=0.005) and younger age (p=0.011). This model was adjusted by glucocorticoid dose, immunosuppressive therapy, disease duration, age, and MIF, adiponectin, leptin, and resistin levels. The R2 and adjusted R2 of this model were 0.41 and 0.40, respectively.
We tested for interactions in the multiple regression analysis to assess weighted variables associated with the amount of proteinuria (data not shown). After testing for interactions, we identified an interaction between age and adiponectin levels as well as an interaction of serum MIF and adiponectin levels with the amount of proteinuria in SLE patients. In the interaction model, higher adiponectin levels and higher age increased proteinuria levels. Lower MIF levels interacted with higher adiponectin levels to increase proteinuria. The adjusted R2 of the final interaction model was 0.41 with p<0.001.