Predictors of proteinuria, amyloidosis and kidney failure in familial Mediterranean fever: data from the International AIDA Network Registry

Key Information
Year
2025
summary/abstract

Abstract

Objectives: Proteinuria, amyloidosis, and kidney failure are the main long-term renal complications of familial Mediterranean fever (FMF). This study assesses their risk factors, independent of ethnicity or residence.

Material and methods: Patients' data were drawn from the International AIDA Network registry for monogenic autoinflammatory diseases.

Results: A total of 598 FMF patients were enrolled, with 80 having proteinuria, 61 amyloidosis, and 25 kidney failure. At multivariate regression analysis, proteinuria was associated with out-of-flares thrombocytosis (OR: 4.78, 95%CI 1.54-14.8, p=0.007), increased out-of-flares erythrocyte sedimentation rate (ESR) (OR: 2.7, 95%CI 1.3-5.6, p=0.008), homozygous M694V mutation (OR: 2.27, 95%CI 1.1-4.66, p=0.025), and heterozygous M694V mutation (OR: 0.29, 95%CI 0.09-0.86, p=0.026); amyloidosis was associated with the disease duration (OR: 1.034, 95% CI1.004-1.065, p=0.027), during-flares anemia (OR: 2.9, 95%CI 1.18-7.19, p=0.021), out-of-flares leukocytosis (OR: 7.47, 95%CI 1.6-34.7, p=0.01), increased out-of-flares ESR (OR: 3.6, 95%CI 1.48-8.81, p=0.005), and heterozygous M694V mutation (OR: 0.18, 95%CI 0.035-0.9, p=0.04); kidney failure was associated with the age at diagnosis (1.04, 1.0003-1.19, p=0.048), the disease duration in years (OR: 1.07, 95%CI 1.02-1.12, p=0.005), attack frequency per year (OR: 1.04, 95%CI 1.007-1.076, p=0.019), anemia out-of-flares (OR: 4.7, 95% CI: 1.004-22.1, p=0.049), and out-of-flares leukocytosis (OR: 25.8, 95%CI 2.75-242, p=0.004). The intraclass correlation coefficient related to ethnicity and country of residence was 6.7% and 6.8% for amyloidosis, respectively, and 0% for proteinuria and kidney failure.

Conclusions: FMF patients with older age at diagnosis, longer disease duration, anemia, leukocytosis, thrombocytosis, elevated ESR, and homozygous M694V mutation are at higher risk of kidney complications.

Keywords: FMF; complications; kidney; outcome; prognosis.

DOI
10.1093/rheumatology/keaf181.
Authors
Antonio Vitale 1 2, Valeria Caggiano 1 2, Jessica Sbalchiero 1 2, Abdurrahman Tufan 3, Ezgi Deniz Batu 4, Gaafar Ragab 5 6, Piero Portincasa 7, Giovanni Conti 8, Emma Aragona 9, Jurgen Sota 1 2, Francesco Gavioli 1 2, Carla Gaggiano 1 2, Amato De Paulis 10 11, Ali Şahin 12, Maria Cristina Maggio 13, Donato Rigante 14 15, Alma Nunzia Olivieri 16, Derya Yildirim 3, Hamit Kucuk 3, Riza Can Kardas 3, Ibrahim Vasi 3, Seza Ozen 4, Yelda Bilginer 4, Seher Sener 4, Hulya Ercan Emreol 4, Ayman Abdel-Monem Ahmed Mahmoud 5, Mahmoud Ghanema 5, Amina Maher 5, Moustafa Ali Saad 5, Nour Jaber 7, Mohamad Khalil 7, Agostino Di Ciaula 7, Ludovica De Palma 8, Renata Cuzzola 8, Andrea Affronti 9, Fabrizio Gambino 9, Francesca Della Casa 10 11, Ilaria Mormile 10 11, Arif Babayiğit 12, Neşe Çabuk Çelik 12, Maria Francesca Gicchino 16, Karina Jahnz-Rozyk 17, Francesco La Torre 18, Antonella Insalaco 19, Andreas Recke 20, Emanuela Del Giudice 21, Patrizia Barone 22, Marco Cattalini 23, Antonio Luca Brucato 24, Daniela Opris-Belinski 25, Petros P Sfikakis 26, Francesca Li Gobbi 27, Giacomo Emmi 28 29, Henrique A Mayrink Giardini 30, José Hernández-Rodríguez 31, Paola Parronchi 32, Piero Ruscitti 33, Stefania Costi 34, Samar Tharwat 35 36, Anastasios Karamanakos 37, Paolo Sfriso 38, Alessandro Conforti 39, Elena Verrecchia 15 40, Giuseppe Lopalco 41, Benson Ogunjimi 42 43 44 45, Ewa Wiesik-Szewczyk 17, Alberto Balistreri 46, Claudia Fabiani 47 2, Bruno Frediani 1 2, Luca Cantarini 1 2