Soluble urokinase plasminogen activator receptor is a marker of dysmetabolism in HIV‐infected patients receiving highly active antiretroviral therapy

Abstract

Circulating soluble urokinase plasminogen activator receptor (suPAR) reflects the immune and pro-inflammatory status of the HIV-infected patient. Highly active antiretroviral therapy (HAART) suppresses suPAR. Independent of the immune response to HAART, suPAR remains elevated in some HIV-infected patients, reflecting possibly a low-grade pro-inflammatory state. Low-grade inflammation has been implicated in insulin resistance and other features of dysmetabolism. Accordingly it is hypothesized that circulating suPAR is associated with the metabolic status of HIV-infected patients on HAART. Fasting plasma suPAR was determined in 36 normoglycaemic HIV-infected patients on HAART (n = 18 lipodystrophic, and n = 18 non-lipodystrophic) who had estimated insulin sensitivity (Rd) and non-oxidative glucose disposal (NOGM) by euglycaemic hyperinsulinaemic clamps, indirect calorimetry, and glucose tracer infusion. Five patients had circadian suPAR concentrations measured (24 hr, 20 min-intervals). suPAR and non-HDL-cholesterol were higher and Rd, NOGM, and limb fat were lower in lipodystrophic patients than in non-lipodystrophic patients (P < 0.05). suPAR correlated positively with non-HDL-cholesterol and inversely with Rd, NOGM and limb fat (P < 0.005, n = 36). suPAR also correlated positively with leukocyte count and TNF-alpha (P < 0.01, n = 36) but not with IL-6. In multiple regression analyses suPAR was a stronger predictor of dysmetabolism than TNF-alpha and IL-6. Circadian suPAR did not systematically fluctuate. In conclusion, suPAR may reflect the metabolic status of the HIV-infected patient on HAART, thus linking low-grade inflammation, immune constitution, lipid and glucose metabolism, and fat redistribution. Circadian suPAR concentration appeared stable, suggesting that sampling schedule does not affect measurement. Further studies addressing whether suPAR predicts lipodystrophy and dysmetabolism in HIV-infected patients are warranted.

Soluble urokinase plasminogen activator receptor in plasma is associated with incidence of CVD. Results from the Malmö Diet and Cancer Study

“…suPAR was only moderately correlated with the non-specific inflammatory markers hsCRP and WBC which is consistent with other studies 11,22 In terms of ROC-statistics, suPAR showed somewhat weaker relationships with CVD than hsCRP (0.54 vs 0.57). However, the weak correlation between suPAR and other inflammatory markers suggest that suPAR represents a separate pathway and therefore could add further prognostic information.…”

Soluble urokinase plasminogen activator receptor levels reflect organ damage in systemic lupus erythematosus

“…Many cytokines and routine laboratory measures were associated with suPAR (Table 2). Convincing correlations between suPAR and the proinflammatory cytokines IL-1 and TNF as well as CRP and creatinine have been shown also in other conditions, 29,[41][42][43] and could be expected since uPAR is up-regulated and shed from immune cells during inflammation. Interestingly, suPAR levels were not inversely associated with complement proteins or complement function, which further demonstrates a lack of apparent association between suPAR and disease activity in lupus.…”

“…41 Thus, it is likely that the absence of a general increase in suPAR levels among SLE patients could be a reflection of decreased leukocyte count (Figure 1). Many cytokines and routine laboratory measures were associated with suPAR (Table 2).…”

The role of suPAR in kidney diseases

“…Unlike other markers (e.g. CRP), its levels either do not undergo circadian variations at all or they are minimal (assayed each 20 minutes for 24 hours) [67]. Its concentration is stable, even in the case of repeated freezing and thawing of serum samples [68].…”