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Study investigates sickle cell disease, decline in eGFR, CKD
Patients with sickle cell disease present with a more rapid decline in eGFR over time, which may provide markers for associated comorbid conditions and disease severity, according to a study published in the American Journal of Kidney Diseases.
“The results of our study demonstrate that patients with sickle cell disease, particularly those with the more severe forms of sickle cell disease (sickle cell anemia [HbSS disease] or Sickle B0 thalassemia), have rapid loss of kidney function over time,” lead author, Vimal Derebail, MD, MPH, FASN, told Healio Nephrology. “Chronic kidney disease is common in this population as well. In patients with mild forms of sickle cell disease (hemoglobin SC Disease and sickle B+ thalassemia), diabetes – a traditional kidney disease risk factor – was associated with loss of kidney function over time.”
He added, “We did note that patients with chronic kidney disease were more likely to have been on angiotensin converting enzyme-inhibitors and angiotensin receptor blockers (ACE-I/ARBs), drugs usually used to delay loss of kidney function. However, rather than causing CKD in these patients, we believe they were simply more likely to have been prescribed these drugs since they had CKD or were at higher risk for it.”
In this retrospective observational study of 427 adults with sickle cell disease (SCD), researchers studied the presence of CKD, proteinuria on urinalysis, current kidney transplant or dialysis at baseline, change in eGFR and presence of proteinuria with time. Patients had measurements taken in a single center from 2004 to 2013, according to the study. Researchers used the baseline visit as the first serum creatinine measurement.
Of the 427 patients, 331 had two or more creatinine measurements taken, with a median follow-up of 4.01 years. Researchers found the annual eGFR decline was 2.05 mL/min/
1.73 m2 for severe genotypes and 1.16 mL/min/1.73 m2 for mild genotypes. Additionally, it was observed that eGFR levels were inversely proportional to hemoglobin levels in patients with SCD and CKD, within the severe genotype subgroup. None of the study variables appeared to be associated with proteinuria over time, according to the study results.
“Microinfarction and worsening hypoxia trigger additional prostaglandin release and subsequent vasodilation, increasing renal blood flow,” the authors wrote. “As a result, GFR first increases, manifesting in pathologic hyperfiltration and eventually producing albuminuria or overt proteinuria, glomerular sclerosis and subsequently reduced eGFR. Endothelial dysfunction, driven by endothelin 1 level elevation, increased soluble fms-like tyrosine kinase 1 level, and hemolysis, also likely contributes to CKD.”
Researchers concluded that hemoglobinuria was associated with CKD, when adjusting for patient age and sex. Adult patients with SCD presented with an accelerated decline in eGFR over time. The GFR decline in patients with severe genotypes was greater than investigators had previously expected, in otherwise healthy individuals. According to the study, this magnitude of loss is comparable to that of older patients with diabetes.
“Future research needs to focus on systematically obtaining measures of kidney function and proteinuria so that we can more precisely understand which patients are at greater risk and whether we can develop interventions specific to preventing kidney disease and/or slowing loss of kidney function,” Derebail said. – by Scott Buzby
Reference:
www.ajkd.org/article/S0272-6386(19)30007-1/abstract
Disclosures: The authors report no relevant financial disclosures.
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Derebail V, et al. Am J Kidney Dis.2018;doi:10.1053/j.ajkd.2018.12.027.