Family History in the Context of CKD

Background: A family history of health conditions may reflect shared genetic and/or environmental risk. It is not well known to what extent family history impacts outcomes among patients with chronic kidney disease (CKD). Herein, we studied the associations of family history of CKD, diabetes, and other conditions with common comorbidities and kidney disease progression among patients with CKD. Methods: We carried out an observational study of two prospective CKD cohorts, 2,573 adults and children from the Cure Glomerulopathy Network (CureGN) and 3,939 Chronic Renal Insufficiency Cohort (CRIC) adult participants. Self-reported first-degree family history of CKD, diabetes, and other common diseases were tested for associations with the risk of comorbidities and CKD progression using multivariable models. Results: Family history of common comorbid conditions was associated with higher risk of these conditions in the context of CKD, including approximately by over 3-fold for diabetes (adjusted OR 3.37, 95% C.I. 2.73-4.15), 48% for cancer (adjusted OR 1.48, 95% C.I. 1.05-2.09), and 69% for cardiovascular disease (adjusted OR 1.69, 95% C.I. 1.36-2.10 in combined cohorts). While polygenic risk score for CKD was associated with kidney disease progression (adjusted HR 1.11, 95% C.I. 1.06-1.16 in combined cohorts), family history of kidney disease was not an independent risk factor for disease progression in the context of existing CKD. In contrast, family history of diabetes was significantly associated with a higher risk of CKD progression independently of diabetes occurrence, or polygenic risk score for diabetes (adjusted HR 1.19, 95% C.I. 1.05-1.35 in combined cohorts). Conclusions: Broad collection of family history in the context of CKD improved clinical risk stratification. Family history of diabetes was consistently associated with a higher risk of CKD progression independently of diabetes status or polygenic risk score for diabetes in both cohorts.