Clinical phenotypes and long-term outcome of kidney involvement in Erdheim-Chester histiocytosis

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that frequently infiltrates the peri-kidney space (hairy kidney appearance), kidney pelvis and proximal ureters, leading to obstructive uropathy. Here, we analyzed the clinical characteristics, imaging findings and long-term kidney outcome of a large multicenter cohort comprising 195 consecutive patients with ECD. Retroperitoneal peri-kidney or peri-ureteral involvement was detected at diagnosis in 147 patients. Of them, 70 had hydronephrosis (bilateral in 47), and 16 with kidney atrophy (unilateral in 14). Kidney vascular peduncle infiltration was found in 60 patients, and kidney artery stenosis in 31. The estimated glomerular filtration rate (eGFR) at diagnosis was significantly lower in patients with than in those without peri-kidney involvement (median 74 vs. 98 mL/min/1.73 m(2)). Ureteral stenting often failed to achieve kidney function recovery. A total of 181 patients received medical therapies: first-line treatments included interferon -a(61%), BRAF-inhibitors (17%), mTOR-inhibitors (7%), or other drugs (15%). These therapies were efficacious for ECD but rarely induced kidney function improvement (one-year eGFR increase over 25% in under 10% of patients). After a median of 43 months, 19% of patients died and 5% developed kidney failure. Among patients with peri-kidney involvement, 44% developed chronic kidney disease (CKD) 3-5 at five years vs. 5% of those without. Unadjusted predictors of advanced CKD and kidney failure/death were age over 50 years, hypertension, BRAFV600E mutation, and baseline eGFR. At multivariable analysis, cardiovascular comorbidities were associated with advanced CKD, and age over 50 years with kidney failure/ death. Thus, kidney involvement is common in ECD and can lead to CKD or kidney failure despite effective medical therapies or urological procedures.

Automated summary

Erdheim-Chester disease (ECD) is a rare condition that can cause kidney involvement and obstructive uropathy. In this study, the clinical characteristics, imaging findings, and long-term kidney outcomes of 195 ECD patients were analyzed. Kidney involvement was common, and patients with peri-kidney or peri-ureteral involvement had a higher risk of developing chronic kidney disease and kidney failure. Medical therapies were effective for ECD but had limited impact on improving kidney function. The study highlights the importance of monitoring and managing kidney complications in ECD patients.