Association of Chronic Kidney Disease With Risk of Intracerebral Hemorrhage

Abstract

IMPORTANCEThe evidence linking chronic kidney disease (CKD) to spontaneous intracerebral hemorrhage (ICH) is inconclusive owing to possible confounding by comorbidities that frequently coexist in patients with these 2 diseases. OBJECTIVE To determine whether there is an association between CKD and ICH risk. DESIGN, SETTING, AND PARTICIPANTSA 3-stage study that combined observational and genetic analyses was 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.

Renal and Electrolyte Disorders and the Nervous System

“…Compared with no renal impairment, an eGFR less than 60 mL/min/1.73 m 2 was independently associated with an increased presence and burden of cerebral microbleeds 33 . In a retrospective cohort study, eGFR and ICH showed an inverse stepwise relationship, where hemorrhage risk increased by 9% for every 10-mL/min/1.73m 2 decrease in eGFR 34 . This stepwise relationship persisted even after adjustment for albuminuria, use of antiplatelet and anticoagulant therapies, and other medical comorbidities.…”

“…22 CHRONIC KIDNEY DISEASE AND INTRACEREBRAL HEMORRHAGE Chronic kidney disease is independently associated with a greater risk for intracerebral hemorrhage (ICH) and poorer functional outcome after the event (CASE 5-2). 33,34 The increased risk of ICH in chronic kidney disease is present for lobar and nonlobar hemorrhages, as well as cerebral microbleeds that may act as a source for future hemorrhagic events. For patients with ICH, an eGFR less than 45 mL/min/1.73m 2 was associated with a threefold increase in hematoma volume CASE 5-1 A 78-year-old woman with a past medical history of poorly controlled hypertension, hypertensive nephropathy requiring chronic dialysis, and left subcortical ischemic stroke 1 year before presented with 5 days of progressively worsening mental status.…”

“…Chronic kidney disease is independently associated with a greater risk for intracerebral hemorrhage (ICH) and poorer functional outcome after the event ( case 5-2 ) 33,34 . The increased risk of ICH in chronic kidney disease is present for lobar and nonlobar hemorrhages, as well as cerebral microbleeds that may act as a source for future hemorrhagic events.…”

“…Klotho protein deficiency, hyperphosphatemia, and nitric oxide deficiency may contribute to shared small vessel disease in both the kidneys and brain. Urine albumin-to-creatinine ratios have been associated with an increased ICH risk 34 . Cerebral small vessel disease may lead to increased vessel fragility and ICH risk over time.…”

Chronic kidney disease promotes cerebral microhemorrhage formation

“…Chronic kidney disease (CKD) is a major public health issue that affects 15% of U.S. adults, leading to impaired quality of life [ 1 ]. Meta-analysis and systemic review of population-based studies provide strong evidence supporting CKD as an independent risk factor for cerebral small vessel disease and cognitive impairment [ 2 – 4 ]. Notably, end-stage renal disease is associated with a substantially higher risk of both ischemic and hemorrhagic strokes [ 3 ] as well as accelerated brain aging and cognitive decline [ 5 ], and consequently, higher morbidity and mortality [ 6 ].…”