Julie Belliere

Pour s’affranchir de la biopsie rénale, qui reste invasive, de nombreux biomarqueurs urinaires ont été étudiés pour détecter, stratifier et prédire la progression des patients atteints de maladie rénale aiguë ou chronique. Appréhendés sous le terme de « biopsie liquide », certains de ces candidats moléculaires (protéiques ou peptidiques) sont robustes et prometteurs. Cette revue détaille ce qu’est un biomarqueur ainsi que les étapes de son développement, en se basant sur des exemples concrets : signatures aussi bien pronostiques (dans les anomalies du développement rénal anténatal ou la prédiction de l’insuffisance rénale aiguë) que diagnostiques (pour des contextes récurrents comme les glomérulopathies avec le CD163 soluble urinaire, les néphrites interstitielles aiguës avec le CXCL9). Les techniques de dosage y sont également décrites. Les biomarqueurs les plus avancés peinent à dépasser la validation externe multicentrique en raison de limitations méthodologiques inhérentes aux technologies et aux cohortes hétérogènes. En 2026, ces biomarqueurs demeurent avant tout des outils d’investigation, dont l’utilisation n’est pas encore consensuelle.

Background: Immune checkpoint inhibitor (ICI)–associated acute interstitial nephritis (ICI-AIN) has emerged as a common cause of acute kidney injury (AKI). However, acute tubular necrosis (ATN) may present with similar clinical features yet requires fundamentally different management. Robust data on the prevalence of ATN among patients with suspected ICI-AIN are limited. The aim of this study was to determine the prevalence of ATN in patients with suspected ICI-AIN and to estimate the risk of diagnostic error associated with empirical corticosteroid therapy in the absence of kidney biopsy. Methods: We conducted a retrospective multicenter study including ICI-treated patients who developed AKI and underwent kidney biopsy. Patients with glomerular presentations were excluded. Based on histopathological findings, patients were classified into two groups: ICI-AIN and isolated ATN. The primary outcome was the prevalence of ATN among patients with suspected ICI-AIN. Secondary outcomes included the description of clinical characteristics, concomitant medications, and laboratory findings, as well as the identification of factors potentially distinguishing ATN from ICI-AIN. Results: A total of 132 patients were included. ICI-AIN was diagnosed in 76 patients (58%), while isolated ATN was identified in 56 patients (42%). Among subgroups with known risk factors for ICI-AIN, isolated ATN was observed in 20% (7/35) of patients exposed to proton pump inhibitors (PPIs), 23% (3/13) receiving combination ICI therapy, 31% (5/16) with pre-existing chronic kidney disease (CKD), and 34% (10/34) with concomitant extrarenal immune-related adverse events (irAEs). ATN was also present in 23% (6/26) of patients treated with ICI monotherapy. Patients with AIN had more severe renal impairment, with a higher median serum creatinine level at presentation (200 µmol/L vs. 141 µmol/L, p < 0.001). Leukocyturia and hematuria were significantly more frequent in the AIN group (p = 0.007 and p = 0.009, respectively). PPI use was significantly more common in patients with AIN than in those with ATN (40% vs. 19%, p = 0.027), whereas exposure to platinum-based chemotherapy was more frequent in the ATN group (78% vs. 59%, p = 0.027). Conclusion: Although certain clinical features are associated with ICI-AIN, they are insufficient to reliably differentiate it from ATN without histological confirmation. An empirical management strategy involving corticosteroid therapy without kidney biopsy carries a diagnostic error risk of approximately 40%, underscoring the importance of kidney biopsy as the diagnostic gold standard.

Objectives: This study aims to assess urinary soluble CD163 normalized to creatinuria (usCD163/Cre) alongside conventional biomarkers as indicators of renal activity and therapeutic response in LN. Methods: A monocentric and retrospective cohort analysis involving 214 patients with SLE was conducted, among whom 129 were referred as LN and assessed longitudinally. Of these, 39 underwent kidney biopsy at sample collection. Data were extracted from medical records, including metrics on renal activity (SLEDAI-R), histological characteristics and therapeutic response according to KDIGO 2024 outcome criteria. The characteristics of usCD163/Cre (ELLA-G2) were compared against routinely used biomarkers and confounding factors including renal function and concomitant medication use. Results: The cross-sectional analysis indicated that usCD163/Cre [area under the curve (AUC) = 0.999], spot urine protein/creatinine ratio or PCR (AUC = 0.994) and serum albumin levels (AUC = 0.940) distinguished between active LN and inactive states, and correlated with SLEDAI-R scores. At the time of kidney biopsy, usCD163/Cre was the only reliable predictor of histological activity (AUC = 0.962; threshold 1200 ng/mmol). During follow-up assessments, usCD163/Cre outperformed PCR to discriminate disease flares (>520 ng/mmol), and categorization into low (1200 ng/mmol) usCD163/Cre levels at 3 and 6 months, following therapy introduction, allows to predict complete, partial and non-responders as an independent factor. Conclusion: Our findings support the involvement of CD163 positive macrophages (M2c) in the pathophysiology of LN and advocate for the inclusion of usCD163/Cre measurement in the standard of LN management to assess LN flare episodes and as an early predictor of therapy response.

Background: Acute interstitial nephritis (AIN) is the most common renal immune-related adverse event after immune check-point inhibitors (ICI). We hypothesized that alternatively activated macrophages (CD163-M) could be involved in ICI-AIN and wished to evaluate the use of their soluble urinary form (us)CD163 as a non-invasive diagnostic marker. Methods: CD163-M infiltrates were evaluated by both immune-histochemistry and multiplex immunofluorescence and imaging. usCD163 was detected with ELLA technology and evaluated together with urinary creatinine to be expressed as a ratio to creatinuria in ng/mmol. Clinical data were collected to perform correlations with renal function assessed by estimated glomerular filtration rate (eGFR). Results: A retrospective cohort of 63 ICI-exposed patients with tubular acute kidney injury profile requiring a biopsy were selected. AIN patients (n = 44) were compared to acute tubular necrosis (ATN) patients (n = 19). CD163-M staining was detectable in all ICI-AIN patients, which was significantly higher than in ATN patients (18.4% vs 3.6% of area, P = .005). CD163-M staining was restricted to the interstitial compartment. CD163-M infiltrate inversely correlated with initial eGFR (r = −0.6, P = .003), and was positively correlated with delta eGFR, reflecting a renal improvement outcome (r = 0.48; P = .02). usCD163 was well detected in urines of patients, but did not allow us to distinguish ATN from AIN patients at diagnosis. No correlation was observed, neither between usCD163 and CD163-M staining nor with renal response after 3 months of glucocorticoid tapering. Conclusion: CD163-M are detected in ICI-AIN and correlate both with severity at diagnosis and better prognosis at 3 months. CD163-M may help us to distinguish AIN from ATN but, it does not allow us to assess ICI imputability. Although detected in urine, usCD163 is clearly not a surrogate biomarker for AIN diagnosis.