Hydroxyurea May Improve Sickle Cell Nephropathy in Adults with HbSS
Authors: Alan Sheinei , Fusisi Rania , Marti Sebasitan Mendez , Zik Chad , Ershler William B 
Published: June 2024

Abstract

Presentation Date: 6/9/2024
Presentation Start Time: 2:09:00 PM

Background
Sickle cell nephropathy (SCN) is a common complication in individuals with sickle cell disease (SCD), characterized by kidney damage and impaired function. Presently, it is estimated that up to 30% of children and 60% of adults may have signs of sickle cell related kidney complications, particularly microalbuminuria. Sickle cell nephropathy is dysregulated glomerular filtration with subsequent increase in urinary protein, defined as urine microalbumin greater than 30 ug/mg. SCN is ubiquitous and one of the most profound silent end organ damage complications of SCD. Its high prevalence in adults make it an important target for disease control.
In our clinical cohort, of 131 screened patients, 48 patients (∼36%) SCN defined by a urine microalbumin to creatinine ratio surpassing 30 ug/mg. Given the nascent establishment of our center, the majority of adults underwent this assessment during the initial intake phase, reflecting a cohort previously lacking comprehensive care. Within this demographic, our scrutiny delved into the nuanced impact of hydroxyurea (HU), especially among individuals who, upon establishing care, exhibited either no prior exposure or inconsistent utilization of HU. Rigorous educational interventions elucidated the multifaceted role of HU and its global impact. Tracking patients' renal and hematologic parameters and urine microalbumin levels over an extended timeframe revealed a dynamic interplay. This abstract, elucidating our findings, underscores a noteworthy correlation between the initiation or consistent use of HU and the amelioration of microalbuminuria, thereby emphasizing its potential renoprotective effects in this population.

Methods
Adult sickle cell patients who were either new to our center or had limited prior exposure to comprehensive SCD care underwent extensive education on disease-modifying therapies, with a specific focus on HU. Upon initiation or resumption of HU treatment for each patient, a comprehensive monitoring protocol was implemented. This involved closely tracking hematologic parameters and urine microalbumin levels. During the initial phase of HU introduction, patients were subject to monthly follow-up assessments to facilitate adaptation to the medication and to ensure appropriate responses. Each monthly visit involved the monitoring of key hematologic parameters, including total hemoglobin, hemoglobin F and markers of hemolysis. Furthermore, a meticulous examination of urine microalbumin levels was performed both before the initiation of hydroxyurea and once patients reached an optimal dose of the medication. This systematic approach allowed for a comprehensive evaluation of the impact of HU on various clinical indicators, contributing valuable insights to our study.

Results
In our clinical cohort of 131 actively screened patients, a notable 36% exhibited evidence of SCN. Within this subset, a focused examination was conducted on eight adults with HbSS characterized by either no prior exposure to HU or inconsistent usage. The observed outcomes revealed a remarkable reduction in urine microalbumin for each individual (Figure 1). Upon aggregation of data, a collective percentage change of approximately 76% was documented, representing a shift from an initial total urine microalbumin level of approximately 298 ug/mg to an improved level of 70 ug/mg (Figure 2). This favorable modulation of urine microalbumin with HU therapy was concomitant with a notable enhancement in hemoglobin F levels, escalating from an average of 9.1% to 13.2%. Concurrently, an improvement in hemoglobin levels was evident, advancing from 7.9 g/dL to 8.7 g/dL on average. Noteworthy improvements were also discerned in hemolysis markers, as reflected by a reduction in average lactate dehydrogenase (LDH) levels from 652 U/L to 551 U/L and a decline in total bilirubin levels from 3.4 umol/L to 2.5 umol/L. These findings collectively underscore the multifaceted positive impact of hydroxyurea on both renal and hematologic parameters in this specific patient cohort.

Conclusions
Our observation not only reaffirms the high prevalence of SCN within the adult sickle cell population but also contribute novel insights to the intricate landscape of conflicting literature regarding the impact of hydroxyurea in the renal system. We demonstrate that aggressive introduction of hydroxyurea in adult HbSS patients may improve microalbuminuria independent of other renoprotective agents including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs).
Effect of Hydroxyurea on Microalbuminuria