Supplementary Material for: Plasma IL-22 predicts progression of early diabetic kidney disease

Introduction. The residual risk of chronic kidney disease (CKD) progression remains high in clinical trials of kidney protective drugs in patients with diabetic kidney disease (DKD).
Methods. In a prospective study, we assessed whether 16 plasma and 10 urine cytokine levels can inform the residual risk of CKD progression in 93 incident patients with DKD treated by Nephrology according to clinical guidelines.
Results. Plasma and urine levels of 12 plasma and 7 urinary cytokines differed between patients with DKD and from healthy controls. Participants were categorized into CKD G1-G2 (preserved GFR) and CKD G3-G5 (GFR <60 ml/min/1.73 m2). After a median of 7.27 years (IQR; 5.34-9.56), 13/40 (32.5%) patients with CKD G1-G2 at baseline had progressed to CKD G3-G5. Progressors had higher plasma IL-22 and TNF-α levels than non-progressors. Plasma IL-22 and TNF-α levels in progressors were similar to those in patients already in CKD G3-G5 at baseline, suggesting that cytokine dysregulation precedes CKD progression. In patients with CKD G1-G2, cut-off points for plasma IL-22 and TNF-α predicted progression with an AUC of 0.76 and 0.77, respectively. Additionally, patients with CKD G1-G2 and plasma TNF-α or IL-22 levels equal to or above the cut-off value had significantly lower eGFR values at the end of follow-up and had more frequently progressed to a very high risk KDIGO category. In cluster analysis, clusters displaying the highest urinary or plasma cytokine levels were associated with worse GFR outcomes.
Conclusion. Plasma IL-22 and TNF-α may help to identify patients with early DKD with a high residual risk of CKD progression despite treatment.