Managing Kidney Disease in Patients with Sickle Cell Disease: A Quality Initiative at the Cleveland Clinic

Background Sickle cell disease (SCD) when complicated by sickle cell nephropathy and chronic kidney disease (CKD) is associated with high morbidity and mortality. Early intervention with appropriate specialist care and timely evaluation for transplant are essential to improve outcomes. There is considerable variability in the screening, diagnosis and management of renal complications in SCD. Current guidelines from the NHLBI (2014), ASH (2019) and expert opinion endorse (1) annual screening for proteinuria, (2) the initiation of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) in patients with significant proteinuria, (3) early involvement of nephrology for declining renal function, (4) testing for alternative etiologies of kidney disease, (5) referral for renal transplant in advanced CKD with regular red cell exchange in those being considered for transplant, and (6) combination therapy with hydroxyurea and erythropoiesis-stimulating agents (ESA) for patients with worsening anemia from CKD. We sought to audit our care of SCD patients along these metrics to devise effective interventions to improve outcomes in SCD patients with comorbid kidney disease.

Methods We conducted a retrospective quality review of renal disease screening, referral, and management in adults with SCD who were seen in the outpatient setting at the Cleveland Clinic in the past 3 years.

Results We reviewed 258 adults with SCD who were seen between July 2019 and July 2022. Of these, 16 patients had insufficient laboratory data and were excluded from further analysis. Our final cohort of 242 patients was comprised of 169 (70%) female patients and the median age was 42 (18-90) years. The majority [213 (88%)] had appropriate screening for proteinuria. Of 46 patients with significant proteinuria, 18 (39%) were on ACEi/ARB in part reflecting challenges with tolerance (hyperkalemia, cough, hypotension). CKD was present in 43 (18%) patients; 25 (58%) had CKD stage 3a, 5 (12%) stage 3b, 6 (14%) stage 4, and 7 (16%) were on dialysis. Nephrology was involved in 27 (63%) of those with CKD. Most [31 (72%)] were evaluated for other causes of CKD, however the extent of testing was inconsistent. Referral for renal transplant evaluation was made in 7 (16%) patients with CKD and approximately half [3 (43%)] of these patients were receiving regular red cell exchange transfusions. Only 2 (5%) patients received a kidney transplant. Of the subset of 13 patients with advanced CKD stages 4 or 5, 9 (69%) were receiving ESA and 3 (23%) were on combination hydroxyurea and ESA.

In our larger cohort of 242, an additional 30 (12%) patients had isolated persistent microscopic hematuria and 44 (18%) patients demonstrated a trend of chronically rising creatinine within the laboratory normal range. Additional analysis is planned to evaluate screening and management in this at-risk cohort with more subtle presentation.

Discussion The management of renal disease in SCD is complex and a paucity of data to support evidence-based guidelines presents a major challenge. We found that rates of screening for proteinuria and declining renal function in SCD patients were high, however the subsequent management was inconsistent. CKD in SCD is highly morbid, and patients with SCD continue to experience low rates of transplant evaluation and eligibility with devastating consequences. A root cause analysis, patient and provider education campaigns, and additional activities are planned to improve the management of kidney disease in patients with SCD.

No relevant conflicts of interest to declare.