{
  "abstract": "Objectives Persistent intrarenal inflammation despite immunosuppression drives kidney damage in lupus nephritis (LN). Current guidelines rely on proteinuria to assess response, though it fails to reflect histological activity in over half of cases. Urinary biomarkers offer a promising noninvasive alternative to monitor histological activity and predict long-term renal outcomes. We evaluated candidate urinary biomarkers previously linked to histological activity and renal function loss in LN patients undergoing per-protocol repeat biopsies one year after treatment initiation.Methods Twenty LN patients from Belgium and Sweden underwent diagnostic and one-year per-protocol kidney biopsies. Treatment was at physician discretion. Urine samples were collected at both time points and analyzed with Olink Explore HT (5416 proteins). Four biomarkers were selected based on prior evidence: IL-16 and soluble CD163 (sCD163) for histological activity, Tenascin C for renal function loss, and BAFF for B cell activity.Results At baseline, 18/20 (90%) patients had ISN/RPS class III or IV ± V LN and 2/20 (10%) pure class V. Paired biopsies were available for 18 patients (16 proliferative); one biopsy was unsuccessful and one patient declined. After one year, 6/16 (37%) transitioned from proliferative to non-proliferative classes, and the NIH Activity Index decreased in all proliferative cases. The Chronicity Index increased in some but the median remained stable. Ten of sixteen (62%) had persistent proliferative LN, though only six (37%) had an activity index >1. Proteinuria did not correlate with histological activity at either time point. Baseline urinary IL-16 and sCD163 correlated with histological activity, particularly in proliferative LN, but these associations diminished at follow-up. In contrast, Tenascin C and BAFF correlated with histological activity at one year.Conclusions Urinary IL-16 and sCD163 reflected macrophage-driven inflammation at diagnosis, whereas Tenascin C and BAFF indicated stromal activation and B cell persistence at one year, suggesting a temporal shift in inflammatory pathways. Although sCD163 predicted future renal function loss, it did not align with one-year histological activity, highlighting differences between urinary and biopsy-based markers. Despite the small sample size, findings support urinary biomarkers as complementary tools capturing molecular disease activity beyond traditional measures.",
  "authors": [
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, USA"
      ],
      "name": "Andrea Fava"
    },
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, USA"
      ],
      "name": "Chen-Yu Lee"
    },
    {
      "affiliations": [
        "Oklahoma Medical Research Foundation, Oklahoma, USA"
      ],
      "name": "Carla Guthridge"
    },
    {
      "affiliations": [
        "Karolinska Institutet and Karolinska University Hospital, Division of Rheumatology, Department of Medicine Solna, Stockholm, Sweden"
      ],
      "name": "Dionysis Nikolopoulos"
    },
    {
      "affiliations": [
        "Karolinska Institutet and Karolinska University Hospital, Division of Rheumatology, Department of Medicine Solna, Stockholm, Sweden"
      ],
      "name": "Julius Linblom"
    },
    {
      "affiliations": [
        "Cliniques universitaires Saint-Luc, Brussels, Belgium"
      ],
      "name": "Farah Tamirou"
    },
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, USA"
      ],
      "name": "Michelle Petri"
    },
    {
      "affiliations": [
        "Oklahoma Medical Research Foundation, Oklahoma, USA"
      ],
      "name": "Joel Guthridge"
    },
    {
      "affiliations": [
        "Cliniques universitaires Saint-Luc, Brussels, Belgium"
      ],
      "name": "Frederic Houssiau"
    },
    {
      "affiliations": [
        "Karolinska Institutet and Karolinska University Hospital, Division of Rheumatology, Department of Medicine Solna, Stockholm, Sweden"
      ],
      "name": "Ioannis Parodis"
    }
  ],
  "title": "PT2:03 Association of urinary biomarkers with histological features in diagnostic and per-protocol repeat kidney biopsies in lupus nephritis",
  "uid": "ddbfa79a-2dfb-5acc-8143-fa310b566278"
}