Comment on: Renal arteriosclerosis in kidney biopsies associated with higher 10-year atherosclerotic cardiovascular disease in lupus nephritis: Reply
Year: 2025
Type: letter
Abstract: Dear Editor, We would like to thank Dr Sener and Sener [1] for their interest in our paper highlighting a novel association between moderate–severe renal arteriosclerosis (ASCL) in kidney biopsies at LN diagnosis and future 10-year clinical atherosclerotic cardiovascular disease (ASCVD) after LN diagnosis [2]. Sener and Sener [1] raised an important question regarding not including albuminuria and uncontrolled low density lipoprotein (LDL) levels (LDL >100 mg/dl) in the primary analysis. While we agree that albuminuria is an ASCVD risk factor, albuminuria is not routinely measured in LN in adults, while overall proteinuria is [3, 4]. We factored in proteinuria in the multivariable analysis, effectively controlling for albuminuria, as albumin makes up a significant proportion of the proteins lost in LN. Next, given that patients with LN are young, we and others have reported that ASCVD risk assessment is often overlooked in LN [5, 6]. Consistent with these findings, in our retrospective cohort, LDL levels at or within 2 years of diagnosis were missing in >50% of the cohort. Therefore, this variable was not included in our primary analysis, and instead we included a more uniformly reported variable, history of hyperlipidaemia, in our primary analysis. To address this concern, we have now completed a sensitivity analysis where we imputed median LDL levels for missing values and categorized as LDL >100 mg/dl at or within 2 years of diagnosis (yes vs no) to indicate dyslipidaemia. In this sensitivity analysis, urine protein creatinine ratio and an interaction term between prior cardiovascular disease (CVD) and LDL >100 mg/dl at or within 2 years of diagnosis were included. Even after controlling for additional variables, moderate–severe renal ASCL remained strongly associated with 3-fold higher 10-year clinical ASCVD occurrence (adjusted HR 2.57, 95% confidence intervals (CIs) 1.10–6.18, P 0.035). A strong interaction between prior CVD before LN and LDL levels >100 mg/dl, and 10-year clinical ASCVD after LN diagnosis was noted in this sensitivity analysis (adjusted HR 9.94, 95% CIs 1.37–72.4, P-value 0.02). However, the clinical relevance of this interaction needs to be ascertained in future prospective studies, as the precision of this estimate was limited (wide CIs) and we had imputed LDL levels for >50% of the cohort.
Source: Lara D. Veeken
Institutions: University of Wisconsin–Madison, The Ohio State University
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4407136108