Mortality and Hospitalizations among Sickle Cell Disease Patients with End-Stage Kidney Disease Initiating Dialysis

Abstract

<b><i>Background:</i></b> Sickle cell disease (SCD) is the most common inherited hematological disorder and a well-described risk factor for end-stage kidney disease (ESKD). Mortality and hospitalizations among patients with SCD who develop ESKD remain understudied. Furthermore, prior studies focused only on SCD patients where ESKD was caused by SCD. We aimed to describe mortality and hospitalization risk in all SCD patients initiating dialysis and explore risk factors for mortality and hospitalization. <b><i>Methods:</i></b> We performed a national observational cohort study of African American ESKD patients initiating dialysis (2000–2014) in facilities affiliated with a large dialysis provider. SCD was identified by diagnosis codes and matched to a reference population (non-SCD) by age, sex, dialysis initiation year, and geographic region of care. Sensitivity analyses were conducted by restricting to patients where SCD was recorded as the cause of ESKD. <b><i>Results:</i></b> We identified 504 SCD patients (mean age: 47 ± 14 years; 48% females) and 1,425 reference patients (mean age: 46 ± 14 years; 49% females). The median follow-up was 2.4 (IQR 1.0–4.5) years. Compared to the reference, SCD was associated with higher mortality risk (hazard ratio 1.66; 95% confidence interval [CI]: 1.36–2.03) and higher hospitalization rates (incidence rate ratio 2.12; 95% CI: 1.88–2.38) in multivariable analyses. Exploratory multivariable mortality risk models showed the largest mortality risk attenuation with the addition of time-varying hemoglobin and high-dose erythropoietin, but the association of SCD with mortality remained significant. Sensitivity analyses (restricted to ESKD caused by SCD) also showed significant associations between SCD and mortality and hospitalizations, but with larger effect estimates. High-dose erythropoietin was associated with the highest risk for mortality and hospitalization in SCD. <b><i>Conclusions:</i></b> Among ESKD patients, SCD is associated with a higher risk for mortality and hospitalization, particularly in patients where SCD is identified as the cause of ESKD.

Patients with sickle cell disease who develop end‐stage kidney disease continue to experience poor survival — A 19‐year United States Renal Data System study

“…2,3 Prior studies suggest the one-year mortality rate after initiating dialysis is higher in patients with SCD but early care by a nephrologist may decrease mortality. 4 Additionally, individuals with ESKD due to SCD (SCD-ESKD) are less likely to receive an arteriovenous fistula (AVF) when initiating haemodialysis (HD) 5,6 despite studies demonstrating improved survival when dialyzed with an AVF or graft. 7,8 Finally, referral for transplantation and transplantation rates are lower among individuals with SCD-ESKD despite the improved survival benefit of kidney transplantation.…”

Sickle Cell Disease and CKD: An Update

“…Combining an ESA with hydroxyurea in SCD patients with CKD may allow more aggressive hydroxyurea dosing in high-risk patients and lead to a greater improvement in Hb concentration compared to ESA alone [121, 125]. One study noted a high erythropoietin dose was associated with an increased risk of mortality and hospitalizations in SCD patients with advanced stages of CKD [126]. Lastly, a new class of agents, the hypoxia inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) is being explored in patients with CKD with or without dialysis dependence.…”

“…These investigators utilized the Centers for Medicare and Medicaid data between the years of 2005 and 2009 and additionally reported a lower death rate in SCD patients who received predialysis nephrology care. The higher mortality in patients with SCD on hemodialysis or peritoneal dialysis continues to be observed in follow-up studies [126, 131]; one study finds a significant association between the need for dialysis with higher mortality risk and hospitalization rates [126]. A recent analysis examining the US Renal Data System (USRDS) over a 19-year period demonstrated that despite prenephrology care, SCD patients on dialysis experienced significantly shorter survival when compared to non-SCD patients (7.0 vs. 12.4 years, respectively) [132].…”

“…Several studies demonstrate that renal replacement therapy is likely to be initiated in patients with SCD with hemodialysis using a central catheter compared to an arteriovenous fistula (AVF) or peritoneal dialysis [38, 126, 131]. Studies in non-SCD patients demonstrate improved survival when dialyzed with an AVF or graft [133, 134].…”

An Overview of Solid Organ Transplantation in Patients With Sickle Cell Disease

“…Patients with SCD have more complications (specifically infections and thrombosis of dialysis access)‚ are admitted to hospital more frequently‚ and are less likely to be offered a kidney transplant. 16,17…”