We initially enrolled 1545 individuals and a total of 1049 were in final analysis after exclusion criteria (Fig. 1). We excluded participants who were missing laboratory results (n =32) and ultrasound results (62), had a history of DM (129), severe CVDs or cancer (17), excessive consumption (male ≥ 140 g/week, female ≥ 70 g/week) of pure alcohol (n = 117), self-reported viral hepatitis (including hepatitis B and hepatitis C virus) (n = 53), was using medications associated with secondary NAFLD or autoimmune liver disease (n = 21), and was considered as secondary hyperuricaemia (8).
Baseline Characteristics of participants with gout
Clinical characteristics of the individuals stratified by the presence of gouty nephropathy were shown in Table 1, and stratified by the severity of NAFLD in Table 2. As shown in Table 1, among the 1049 hospitalized non-diabetic gouty patients, 17.4% were found to have gouty nephropathy. Participants with gouty nephropathy were older and had longer gout duration, more prone to be smokers, with lower BMI, higher SBP, higher FPG and SUA levels, than those without gouty nephropathy. Of note, participants with gouty nephropathy were more likely to have lower prevalence and severity of NAFLD by ultrasound, with lower levels of ALT and AST, than those without gouty nephropathy (P < 0.001). Meanwhile, insignificant differences in sex, DBP, HOMA-IR, and lipid profiles (including LDL-c, HDL-c, TG, TC and FFA) between the groups were detected.
The trend analysis of demographic and biochemical features among different categories of NAFLD severity was presented in Table 2. As we can see, participants with higher severity of NAFLD seem to be younger, more likely to be smokers, with higher BMI and abdominal obesity, higher FPG and HOMA-IR, higher levels of SUA, LDL-c, TG, TC and FFA, and lower levels of HDL-c, than those with less severe or without NAFLD. Of note, preserved renal function were observed in individuals with more severe NAFLD, reflected by lower prevalence of gouty nephropathy, lower levels of indicators of renal damage (SCr, BUN and Cys C), as well as higher levels of eGFR and Ccr, compared to those with less severe or without NAFLD (P < 0.001).
Association of ultrasound‑diagnosed NAFLD with gouty nephropathy
We further determined the renal function based on eGFR and Ccr levels with respect to the degree of NAFLD severity by box plot (Fig. 2 A and B). As we can see, as the severity of NAFLD increased, the levels of eGFR and Ccr were higher (P < 0.001), with the lowest eGFR levels seen in individuals with non-NAFLD and highest eGFR levels seen in those with severe NAFLD. Box plots were also performed to demonstrated the relationship between liver function and eGFR categories (Fig. 2 C and D). Consistently, with the decline of eGFR in gouty participants, we observed that the levels of liver enzymes including ALT and AST decreased (P < 0.001).
As shown in Table 3, the risk of gouty nephropathy was significantly associated with NAFLD severity in the logistic regression analyses. In unadjusted analysis, the OR was 0.336 (95 % CI 0.218–0.517, P < 0.001), 0.320 (95 % CI 0.205–0.510, P < 0.001) and 0.321 (95 % CI 0.218–0.517, P = 0.001), respectively, in participants with mild, moderate, and severe NAFLD compared to those without NAFLD. On further adjustment for age, sex and smoking, NAFLD severity was still significantly associated with the risk of gouty nephropathy, with OR 0.394 (95 % CI 0.254–0.612, P < 0.001), 0.388 (95 % CI 0.245–0.614, P < 0.001) and 0.152 (95 % CI 0.046–0.499, P = 0.002) in participants with mild, moderate, and severe NAFLD compared to those without NAFLD. When further adjusted for metabolic parameters, including obesity, hypertension, hyperglycemia, hyperuricemia, and hyperlipidemia, the association of NAFLD severity with gouty nephropathy was still significant, with OR 0.392 (95 % CI 0.248–0.619, P < 0.001), 0.379 (95 % CI 0.233–0.616, P < 0.001) and 0.148 (95 % CI 0.043–0.512, P = 0.003) in participants with mild, moderate, and severe NAFLD, respectively, compared to those without NAFLD.
Risk factors for gouty nephropathy in the multiple logistic regression analysis
The complex nature of the variables that determine the gouty nephropathy risk was further studied in a forest plot. As shown in Fig. 3, gouty nephropathy was introduced as a dependent variable in the multiple factors logistic regression analysis, using old age (more than 60 years), long gout duration (more than 10 years), smoking, obesity, hypertension, hyperglycemia, hyperuricemia, high LDL-c, low HDL-c, high TG and high TC level, as well as NAFLD severity as independent variables. In addition to the severity of NAFLD, we observed the old age, hypertension, and hyperglycemia were significant risk factors for gouty nephropathy. However, sex, long gout duration, smoking, obesity, hyperuricemia, and dyslipidemia were insignificantly associated with gouty nephropathy in the non-diabetic gouty participants.
Association of SUA with metabolic syndrome and NAFLD in participants with gout
In the present study, we also examined the association between SUA and both metabolic syndrome and NAFLD severity in the gouty population. To detect different clinical significance of hyperuricaemia for metabolic disorders in patients with and without renal insufficiency, we divided the participants into two groups based on the presence of gouty nephropathy, and separately analyzed the association of SUA with both metabolism-related parameters and NAFLD severity. The Spearman correlation coefficients between SUA and metabolism-related parameters were given in Table 4. SUA was significantly associated with BMI (r = 0.200, P < 0.001), WC (r = 0.187, P < 0.001), DBP (r = 0.098, P = 0.004), HOMA-IR (r = 0.131, P = 0.004), LDL-c (r = 0.151, P < 0.001), TG (r = 0.230, P < 0.001), TC (r = 0.160, P < 0.001) and degree of NAFLD severity (r = 0.240, P < 0.001) in participants without gouty nephropathy. However, this association weakened and became insignificant in participants with gouty nephropathy.