ISOLATED C3 HYPOCOMPLEMENTEMIA AS AN EARLY PREDICTOR OF CHRONIC KIDNEY DISEASE IN LUPUS NEPHRITIS

Simeone Andrulli^1*Lucio Manenti²Francesco Reggiani³Isabella Pisani⁴Domenico Giannese⁵Gisella Vischini⁶Giovanni Valsecchi¹Giulia Godeas⁷Giuseppe Gigliotti^8*Pasquale Esposito⁹Paola De Giovanni¹⁰Corrado Murtas¹¹Chiara Casuscelli¹²Sabrina Caruso¹³Michele Rossini¹⁴Giovanni Andrulli¹⁵Marco Quaglia¹⁶FILIPPO AUCELLA¹⁷Andrea Buscaroli¹⁸Giovanni Maria Rossi⁴Francesca Mattozzi¹⁹Brigida Di Renzo²⁰Fulvia Zanchelli²¹Francesca Bruno²²Raffaela Sciri²³Manes Massimo²⁴Domenica Torres²⁵Maurizio Garozzo^26,27Roberta Lazzarin²⁸Valentina Corbani²⁹Francesco Fontana³⁰Marta Calatroni³Monia Incerti⁴Claudia Bini⁶Barbara Infante⁷Pierluigi D'angio'³¹Margherita Di Martino⁹Angelo Rigotti¹⁰Loreto Gesualdo¹⁴

• ¹Associazione Italiana Ricercare per Curare ODV ETS (AIRpC), Lecco, Italy
• ²Ospedale Sant'Andrea, La Spezia, Italy
• ³IRCCS Humanitas Research Hospital, Rozzano, Italy
• ⁴Azienda Ospedaliero-Universitaria di Parma Struttura Complessa di Nefrologia, Parma, Italy
• ⁵Azienda Ospedaliero-Universitaria Pisana Unita Ospedaliera Cardiologia 2, Pisa, Italy
• ⁶Nephrology Dialysis and Renal Transplant Unit, IRRCS Azienda Ospedaliero-Universitaria, Bologna, Italy
• ⁷Nephrology, Dialysis and Transplantation Unit, Department of Biomedical Sciences, Foggia, Italy
• ⁸Presidio Ospedaliero Maria Santissima Addolorata, Eboli, Italy
• ⁹UO Nefrologia, Dialisi e Trapianto. IRCCS Policlinico San Martino, Genova, Italy
• ¹⁰Ospedale degli Infermi di Rimini, Rimini, Italy
• ¹¹Belcolle Hospital, Nephrology and Dialysis Unit, Viterbo, Italy
• ¹²Nephrology and Dialysis Unit, Department of Clinical and Experimental Medicine, AOU “G. Martino”, Messina, Italy
• ¹³Nephrology and Dialysis Unit, ASST Fatebenefratelli-Sacco, Milano, Italy
• ¹⁴Universita degli Studi di Bari Aldo Moro Dipartimento dell'Emergenza e dei trapianti di organi, Bari, Italy
• ¹⁵Universita Bocconi, Milan, Italy
• ¹⁶SCDU Nefrologia e Dialisi, AOU "SS Antonio e Biagio e Cesare Arrigo", Alessandria, Italy
• ¹⁷Fondazione Casa Sollievo della Sofferenza IRCCS, San Giovanni Rotondo, Italy
• ¹⁸Nephrology and Dialysis Unit, Ospedale Santa Maria delle Croci, Ravenna, Italy
• ¹⁹Ospedale Infantile Regina Margherita, Turin, Italy
• ²⁰Ospedale Antonio Perrino, Brindisi, Italy
• ²¹Ospedale Morgagni-Pierantoni, Forli, Italy
• ²²Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
• ²³Nephrology and Dyalisis Unit, S.Maria della Misericordia Hospital, Perugia, Italy
• ²⁴Ospedale Regionale Umberto Parini, Aosta, Italy
• ²⁵Ospedale Pediatrico Giovanni XXIII, Bari, Italy
• ²⁶Presidio Ospadaliero Santa Marta e Santa Venera, Acireale, Italy
• ²⁷Nephrology and Dialysis Unit, Santa Marta and Santa Venera Hospital District, Acireale, Italy
• ²⁸Nephrology and Dialysis Unit, Ospedale San Giacomo Apostolo, Castelfranco Veneto, Italy
• ²⁹Nephrology and Dialysis Unit Sant'Andrea Hospital, La Spezia, Italy
• ³⁰Policlinico, Modena, Italy
• ³¹Maria Santissima Addolorata Hospital, Nephrology and Dialysis Unit, Eboli, Italy

The role of complement in the long-term renal survival of patients with lupus nephritis (LN) remains poorly understood. Recent studies suggest its potential impact; however, long-term data are lacking.This multicenter, observational, retrospective study aimed at investigating the influence of complement levels on long-term renal outcomes in LN patients. We evaluated whether isolated C3 hypocomplementemia (i-LowC3), defined as serum low C3 (≤80 mg/dL) and normal C4 (>10 mg/dL) six months after kidney biopsy is associated with subsequent risk of chronic kidney disease (CKD), End Stage Kidney Disease (ESKD) or death.445 patients with LN were studied (median follow-up 4.9 years). Based on six-month C3/C4 levels, patients were categorized into i-LowC3 (91 patients) and controls (354 patients). Over the first six months, serum C3 and C4 levels increased by a median of 20 mg/dL and 5 mg/dL, respectively. i-LowC3 was significantly associated with twice the risk of a poor outcome, including CKD, ESKD, composite outcome of CKD or death and ESKD or death, with lower survival rates for all these outcomes compared to controls (P < 0.001). Multivariate Cox regression analysis revealed a lower risk of CKD and CKD or death with increases in C3 levels during the first six months, while i-LowC3 was associated with an independent higher risk for these outcomes.The trajectory of serum C3 levels within the first six months appears to predict long-term renal prognosis of LN patients. These findings support the use of i-LowC3 as a low-cost, readily available biomarker to guide early treatment of LN patients.