Chronic organ failure in adult sickle cell disease Elliott Vichinsky UCSF Benioff Children’s Hospital Oakland, Oakland, CA Sickle cell disease is now a chronic adult illness characterized by progressive multiorgan failure, particularly involving the brain and kidney. The etiology is multifactorial; it includes hemolysis and nitric oxide deficiency. As patients age, most experience neurologic insult. Twenty-five percent of older adults have had a clinical stroke and at least half of the population have had a silent infarct, cortical atrophy, and neurocognitive impairment. Periodic screening with neuroimaging and neurocognitive testing is recommended. Identification and correction of modifiable risk factors such as nocturnal hypoxemia, obstructive sleep apnea, and physical exercise programs should be implemented. Patients with neurocognitive impairment require cognitive remediation and educational accommodations. Chronic renal disease occurs in 25% of older adults and results in 50% of their deaths. Renal failure often develops insidiously. It can be prevented or minimized by early screening and treatment of modifiable risk factors including hypertension and microalbuminuria. There is an increasing number of therapeutic options, including inhibitors of the renin angiotensin system, angiotensin-II receptor blockers, endothelin-1 receptor antagonist, and haptoglobin therapy. Patients with sickle cell disease have increased mortality rates from renal failure compared with nonsickle cell patients, in part from a lack of access to early multidisciplinary care, including timely initiation of dialysis and renal transplantation. Learning Objectives • To describe chronic organ damage caused by chronic renal and central nervous system disease (CNS) in adult sickle cell patients • To learn the modifiable risk factors for chronic renal and CNS disease • To discuss the current screening recommendations for chronic renal and CNS disease in adult patients • To review therapies to modify and treat chronic renal and CNS injury Introduction Sickle cell disease (SCD) has changed from a fatal pediatric illness to a chronic adult disease characterized by progressive multiorgan failure. The survival rate for pediatric patients continues to improve. Although individual sickle cell centers report median survival of 58 to 67 years for SCD, the overall survival for adults has made little progress and even decreased in regions.1,2 The etiology for the variation in survival is multifactorial, but clearly influenced by early detection and treatment of multiorgan dysfunction. Decades ago, before the Cooperative Study of Sickle Cell Disease (a landmark natural history study), the median age of death was 14 years. At the completion of the Cooperative Study in 1988, the median age of death was 48 years for women and 42 for men.3 Recently, the National Center for Health statistics published population-based surveillance data for all causes of death among 12 000 patients with SCD. The overall age of death was 43 years for females and 40 years for males. Lanzkron et al found the pediatric survival increased 3% per year between 1999 and 2005.4 In contrast, during the same period, adult survival decreased 1% per year. The poor overall survival in adults is accompanied by deteriorating quality of life and increased morbidity from multiple complications. Although sudden death remains a serious problem in SCD, irreversible chronic organ failure is the primary cause of death and morbidity in most patients. In addition, detected or undetected chronic organ dysfunction is a causal factor in most acute deaths.5 In the Powars et al landmark 40-year observational study of 10 056 patients, half the adults had irreversible organ damage.5 A single organ dysfunction was an independent predictor of mortality and a risk factor for subsequent multiorgan failure. In particular, lung disease, renal failure, and central nervous system (CNS) complications strongly predicted mortality and progressive clinical deterioration. More recently, Telen et al reported that 32% of adults had a history of neurologic disease, which correlated with early mortality.6 Most clinical mortality reports underestimate the central role of chronic organ dysfunction in death. Manci, in analyzing data from 120 autopsies, found evidence of chronic organ failure in 75% of patients but clinically noted in only 25% of the clinical histories.7 Other reports have also noted a marked discrepancy in the pathology reports compared with the clinical observations. The purpose of this report is to highlight the importance of CNS and renal disease in adult sickle cell patients. Brain Stroke The majority of adult sickle cell patients suffer from CNS injury that