Burden of Chronic Kidney Disease in Californians with Sickle Cell Disease

Introduction: Chronic Kidney Disease (CKD) is a known complication of sickle cell disease (SCD). Data from contemporary adult cohorts estimating prevalence and burden of CKD in the aging sickle cell population are limited. We used administrative data from the Sickle Cell Data Collection (SCDC) program to estimate the burden of CKD in adults with SCD in California over a 10-year period. We also report mortality data and examine access to specialized care (hematology and nephrology) for SCD patients with and without CKD.

Methods: This is a retrospective cohort study of Medicaid-enrolled individuals with SCD in California. Data sources included Medicaid claims, Emergency Department, hospitalization data from 2011 to 2020, and vital records data obtained from the California SCDC program. Individuals aged 18 years or older in 2011, meeting either the confirmed SCD case definition, defined as the presence of laboratory confirmation of SCD, or the SCDC probable case definition of 3 or more SCD-coded encounters during any 5-year period were eligible to be included. We ascertained individuals' CKD status (none versus any, the latter encompassing stages 1 through 5, unspecified stage, and End Stage Renal Disease (ESRD)), based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and ICD-10-CM diagnosis codes. Hematologist and nephrologist encounters were identified using the National Provider Identifier (NPI) of the rendering provider. Linked death records were used to identify deaths that occurred during the study period.

Results: We identified 2,992 individuals with SCD who met inclusion criteria, with 2,311 (77.2%) in the non-CKD group and 681 (22.8%) in the CKD group. The mean age of the cohort at the mid-point of the study was 40.1 years. The CKD population was older in age, and the majority (67.9%) were 30-60-years of age, whereas the non-CKD cohort had majority (61.6%) in the 18-40-year age category. Males had a higher prevalence of CKD when compared to females (26.7% vs. 20.4%). The period prevalence of CKD increased from 8% in the 18-29 year group, to 17% in the 30-39 year group, 24% in the 40-49 year group, 44.6% in the 50- 59 year group and 51.1% for the > 60 years age group. The mean age at first recorded CKD code was 48 years, males were significantly (p<0.05) younger at their first recorded CKD code than females, at 46 and 49 years of age respectively. By first recorded CKD code, one third (33.4%) of individuals had stages 1-2, 39% had stages 3-5, and 4% had ESRD. In contrast, by the latest recorded CKD stage in the 10-year period, more than one-third (35%) had CKD stages 3-5, and 40% reached ESRD. By latest CKD stage, males had more ESRD (40.2%) than stage 3-5 (34.7%), while females had similar burden of ESRD and CKD 3-5 at 37.6% and 38.7% respectively. A total of 478 deaths (15.9%) occurred during the study period, with 50.8% of deaths occurring in the CKD cohort. The median age at death was 53 years for the CKD cohort and 43 years for the non- CKD cohorts, possibly indicating that CKD occurred in patients who did not die of other causes at a younger age. When examining access to care, the median number of visits per year with a hematologist was 0.11 and 0 for the CKD vs. entire cohort respectively. The median number of visits per year with a nephrologist for those with CKD was 0. The proportion of individuals with CKD who had zero visits per year with a hematologist or a nephrologist over the study period was 48% and 61% respectively. Individuals with CKD who died during the study period had a significantly lower number of mean annual visits with a hematologist than those who were alive (1.37 vs 1.23, p<0.001) at the end of the study period. Individuals with CKD who died during the study period had a higher number of visits with a nephrologist than those who were alive (1.56 vs. 2.23, p<0.05) at the end of the study period.

Conclusion: CKD poses a significant burden on adults with SCD. In our cohort, males had a higher prevalence of CKD, and the prevalence of CKD increased with age. 40% of individuals with CKD had a latest recorded stage of ESRD. Half of the deaths that occurred during the study timeframe occurred in the CKD cohort. Californians with CKD and SCD had severe restrictions in access to both hematology and nephrology care. Further prospective studies are needed to understand the natural history of CKD in SCD and identify risk factors for progression.