A Cohort Study of Renal Complications in Patients Over the Age of 40 with Sickle Cell Disease
Authors: Thomson Jennifer J , Breen Cormac , Howard Jo 
Published: April 2020

Abstract
Survival data from the United States (US) has shown a median age of death of 42 and 48 years for men and women respectively with HbSS disease, with renal failure being a contributory factor in about 18% of adult deaths (Platt, O.S. et al (1994) Mortality in Sickle Cell Disease – Life Expectancy and Risk Factors for Early Death. NEJM 330; 1639–1644). Renal damage begins early in life, with abnormalities of tubular function reflected by hyposthenuria and glomerular damage which results in hyperfiltration and an increased glomerular filtration rate. Microalbuminuria may develop in childhood and can progress to frank proteinuria. In later life, an apparent return to normal glomerular filtration rates often indicates loss of kidney function which may lead to end stage renal failure (ESRF). Although there are no randomised trials in this area it seems likely that, as in patients with other forms of proteinuric kidney disease, renin-angiotensin system blockade might decrease proteinuria and delay progression of kidney disease. The prognosis for patients with sickle cell disease and ESRF is poor despite dialysis, and it is therefore imperative to detect these patients early if we are to slow or halt their progression to ESRF. A retrospective study was performed at St Thomas’ Hospital to provide a snapshot of the prevalence of renal impairment in patients with sickle cell disease aged 40 or over. The sickle cell disease database was reviewed for the year 2007–2008. Kidney disease was defined as either an estimated glomerular filtration rate (eGFR) of &lt;60mL/min (corrected for race), protein creatinine ratio (PCR) of &gt;50 or persistent microscopic haematuria. Patients who were previously started on an ACE inhibitor due to a previously raised PCR were also included even if the most recent results were within the normal range. 80 patients were included in this study, with a median age of 47 (range 40–75 years). 57.1% had HbSS and 31.4% had HbSC disease. 35 patients (43.8%) had kidney disease according to at least one of the criteria above. 33 patients had a PCR of greater than 50 (8), or were on an ACE inhibitor (25) (indicating a previous PCR &gt;50). 12 patients had a corrected eGFR of &lt;60mL/min and 5 patients had microscopic haematuria. The male to female ratio of those included in the study was 1:3 but this did not differ in those with and without kidney disease. 42.6% with HbSS and 42.3% with HbSC had kidney disease. Patients with hypertension (blood pressure (BP) &gt;140/90mmHg) had a relative risk of kidney disease of 1.73 (95% confidence interval; 1.08 – 2.78). A target BP of &lt;130/80mmHg was set for patients with kidney disease (based on evidence from diabetic nephropathy). Only 18 (50%) patients achieved this target. There was an increased tendency towards retinopathy (34.3% cf. 17.8%; relative risk 1.59; range 0.98 – 2.58) but no other associations, in particular, no association with cerebrovascular disease. In conclusion, almost 50% of patients over 40 years with sickle cell disease have kidney disease, which is greater than the background prevalence in all age US adults of 13.1% (Coresh, J. et al (2007) Prevalence of Chronic Kidney Disease in the United States. JAMA 298 (17): 2038–2047). Due to the poor prognosis of ESRF in patients with sickle cell disease and the contributory effect of renal impairment in all cause mortality, early detection and intervention is critical in further improving the quality of life and life expectancy in the increasingly older population of patients with sickle cell disease. Further trials are required to determine the optimal time to intervene and most effective interventions.