Chronic kidney disease linked with spontaneous intracerebral hemorrhage, finds JAMA study

The evidence linking chronic kidney disease (CKD) to spontaneous intracerebral haemorrhage (ICH) is inconclusive owing to possible confounding by comorbidities that frequently coexist in patients with these 2 diseases.

A study was conducted to determine whether there is an association between CKD and ICH risk.

A 3-stage study that combined observational and genetic analyses were conducted. First, the association between CKD and ICH risk was tested in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a multicenter case-control study in the US. All participants with available data on CKD from ERICH were included. Second, this analysis was replicated in the UK Biobank (UKB), an ongoing population study in the UK. All participants in the UKB were included in this study. Third, mendelian randomization analyses were implemented in the UKB using 27 CKD-related genetic variants to test for genetic associations. ERICH was conducted from August 1, 2010, to August 1, 2017, and observed participants for 1 year. The UKB enrolled participants between 2006 and 2010 and will continue to observe them for 30 years. Data analysis was performed from November 11, 2019, to May 10, 2022.

The outcome of interest was ICH, ascertained in ERICH via expert review of neuroimages and in the UKB via a combination of self-reported data and International Statistical Classification of Diseases, Tenth Revision, codes.

The Results of the study are:

• In the ERICH study, a total of 2914 participants with ICH and 2954 controls who had available data on CKD were evaluated
• CKD was found to be independently associated with a higher risk of ICH
• This association was not modified by race and ethnicity. Replication in the UKB with 1341 participants with ICH and 501 195 controls confirmed this association.
• Mendelian randomization analyses indicated that genetically determined CKD was associated with ICH risk

Thus, in this 3-stage study that combined observational and genetic analyses among study participants enrolled in 2 large observational studies with different characteristics and study designs, CKD was consistently associated with a higher risk of ICH. Mendelian randomization analyses suggest that this association was causal. Further studies are needed to identify the specific biological pathways that mediate this association.

Reference:

Vanent KN, Leasure AC, Acosta JN, et al. Association of Chronic Kidney Disease With Risk of Intracerebral Hemorrhage. JAMA Neurol. Published online August 15, 2022. doi:10.1001/jamaneurol.2022.2299

Keywords:

Association, Chronic, Kidney, Disease, Risk, Intracerebral, Hemorrhage, jama neurology, Kevin N. Vanent, Audrey C. Leasure, Julian N. Acosta, Lindsey R. Kuohn, Daniel Woo, Santosh B. Murthy, Hooman Kamel, Steven R. Messé, Michael T. Mullen, Jordana B. Cohen, Debbie L. Cohen, Raymond R. Townsend, Nils H. Petersen, Lauren H. Sansing, Thomas M. Gill, Kevin N. Sheth, Guido J. Falcone,