Keeping it renal: Results of applying guideline-based management in sickle cell nephropathy Free

Introduction Current guidelines for the treatment of sickle cell nephropathy (SCN) endorse initiating angiotensin-converting enzyme inhibitors or angiotensin receptor II blockers (ACEi/ARB) after two separate, untimed instances of urine albumin to creatinine ratio (UACr) ≥30 mg/g. Additionally, Niss and colleagues (2020) concluded that a high proportion of patients with elevated baseline UACr ≥ 100 mg/g developed persistent albuminuria (PA) and warrant immediate intervention. However, evidence supporting ACEi/ARB use is limited, as is information about uptake of the guidelines (Liem et al., 2019). This study aims to examine the progression of SCN after an elevation in UACr with a focus on real-life application of guideline-based care in a high-volume clinic.

Methods This is a retrospective study of 255 patients ages 19-60 with sickle cell anemia (S/S or S/B- genotype) seen at the Center for Blood Disorders in Augusta, Georgia at least once between 2021 and 2025. Patients were defined as having an instance of microalbuminuria (MA) if they had a random UACr ≥30 mg/g. For these patients, we collected variables including UACr values, creatinine and estimated glomerular filtration rate (eGFR), and documentation of ACEi/ARB prescriptions from medical record data between 1998-2025. We used two-sample t-tests to assess the association between continuous and categorical variables.

Results Of 255 patients with sickle cell anemia, 143 (56.1%) had MA. Patients with MA were significantly older than those without it (p=0.0002), with mean ages of 38.3 and 33.4 years, respectively. Among these 143 patients, 77 (53.8%) were female, and 143 (100%) self-identified as Black/African American. Average age at onset of MA was 31.6 years with a range of 8 to 55 years.

ACEi/ARBs were appropriately prescribed in 85 of the 143 patients with MA. They were considered inappropriate and not prescribed in 53 (37.1%) patients due to resolution of UACr elevation (34), loss to follow up (10), management by other specialists (6), and monitoring for repeat UACr elevation (3). Five patients were considered a “missed opportunity to treat,” meaning that they had evidence of MA on ≥2 occasions but were not offered ACEi/ARB.

Among the 85 patients prescribed ACEi/ARB, 36 had repeat levels within a 12-month period of starting the medication. Of these, 23 (63.9%) saw decreases in their UACr. Initiation of ACEi/ARB had a significant effect (p=0.0339) on average UACr, decreasing from 324.34 to 242.83 mg/g. However, long-term effects of ACEi/ARB on UACr were not found (p= 0.337).

Of the 143 patients with elevated UACr, 88 (61.5%) had ≥1 random UACr level ≥100 mg/g. Of these 88 patients, 71 (80.9%) developed PA, as defined by UACr ≥30 mg/g on most recent testing. Average eGFR was significantly lower in patients with PA (p= 0.0251). Similarly, mean calculated CKD stage was significantly higher in those with PA (p= 0.0101).

Discussion This study assessed patients with elevated UACr, the implementation of guidelines, and results of management. The older average age in patients with a history of MA indicates that age may be a risk factor for its development. We also investigated the potential link between high UACr elevation and development of PA. Our study replicates the finding of PA in 80.9% of patients with one anytime UACr value ≥100 mg/g (Niss et al., 2020). PA was associated with worse CKD stage and lower eGFR. Additionally, UACr remained elevated in most patients treated with an ACEi/ARB.

Although uptake of practice guidelines is frequently unknown and difficult to measure, the providers at this sickle cell clinic have integrated ASH guidelines related to management of renal complications associated with disease progression. This is evidenced by 138 (96.5%) patients receiving appropriate therapy for their clinical situation. To our knowledge, this is the first study evaluating uptake of these guidelines since their advent.

The use of ACEi/ARB to manage elevated UACr was associated with short-term UACr improvement. However, this use was not significantly associated with sustained improvement in UACr. This lack of association may be explained by poor adherence, decreased efficacy of the medication for this purpose, or the significant systemic disease progression that eventually overcomes short-term benefits. Prospective studies focused on adherence and barriers to follow up could help describe the true long-term efficacy of ACEi/ARB in patients with SCN.