eGFR Decline in Patients With Sickle Cell Disease

In this podcast, Santosh L Saraf, MD, discusses the decline of estimated glomerular filtration rate in patients with sickle cell disease as an indicator of kidney disease progression. Dr Saraf presented on this topic at the American Society of Hematology’s 2021 annual meeting.

Additional Resource:

Saraf SL, Han J, Ruiz MA, et al. Defining and predicting rapid eGFR decline in sickle cell disease. Paper presented at: American Society of Hematology's Annual Meeting & Exposition; December 9-16, 2021. Accessed January 19, 2022. https://ash.confex.com/ash/2021/webprogram/Paper147861.html

Santosh L Saraf, MD, is an assistant professor of medicine in the Division of Hematology and Oncology at the University of Illinois in Chicago, Illinois. 

TRANSCRIPTION: 

Leigh Precopio:  Hello everyone and welcome to another installment of Podcasts360, your go‑to resource for medical news and clinical updates. I'm your moderator, Leigh Precopio, with Consultant360.

As many as 50% of all adults with sickle cell disease may experience rapid kidney function decline. Kidney disease in this patient population is often a predictor of adverse health outcomes, such as early mortality.

To better understand rapid kidney decline in patients with sickle cell disease, the authors of a recent study examined the decline of an indicator of kidney function, the estimated glomerular filtration rate, also known as eGFR.

Joining us today is study author, Santosh Saraf, MD, who is an assistant professor of medicine in the Division of Hematology and Oncology at the University of Illinois in Chicago, Illinois. Dr Saraf recently presented on this research at the American Society of Hematology’s 2021 annual meeting.

Thank you so much for joining me today, Dr Saraf. To begin, could you give us a brief overview of your session?

Santosh Saraf:  Kidney disease is a major complication in people with sickle cell disease. What we're seeing is that as people with sickle cell disease are living longer, we're starting to see organ dysfunction as a major problem. This predicts people that have more complications, and also early mortality. So we were focused on how the kidneys are damaged and to understand how rapidly the kidney function declines and potential risk factors for kidney function decline.

We looked at our cohort of a little over 400 patients, with a median follow‑up of 7 years, and tried to understand how rapidly the kidney functions declining and what rate of decline predicts early mortality. Then also looking at genetic, clinical, and laboratory risk factors for the rapid decline.

LP:  What are the key clinical takeaway messages? How can they be implemented into clinical practice?

SS:  Rapid kidney function decline is often defined by the non‑sickle cell disease literature. We don't know if that's quite relevant. Often, a decline of -3 or -5 mls per minute per body surface area is what’s defined.

In our cohort, we saw that both of those rates of decline are common, but a rate of decline of -6 was what was associated with the higher risk of mortality. This threshold might be something that we need to identify as high‑risk people. Our laboratory and clinical risk factors, and genetic risk factors all pointed to hemolysis as being key in predicting people that are going to be at risk for kidney function decline. This is a red blood cell breakdown. We think that, with red blood cell breakdown, there's a lot of toxins that are released like cell‑free hemoglobin and heme, and the kidneys are constantly trying to filter these and process these and this can lead to increased kidney stress.

What we saw was that, things like the sickle cell genotype SS being more severe with more hemolysis. Also, the presence of alpha thalassemia protects you against hemolysis and this protected against kidney function decline. That's what we saw on the genetic side.

For our clinical laboratory risk factors, markers of hemolysis like LDH were associated with more rapid decline.

And then a really important screening tool called the urine albumin concentration or albuminuria. This is something that's often used in people with diabetes to screen for early kidney disease. Our data showed that albuminuria is also a very important screening tool in people with sickle cell disease. This should be checked at least annually, and if it's abnormal, it needs to be monitored more closely.

What we saw was that abnormal albuminuria at greater than 30, greater than 100, or more than 300 are all associated with the higher risk of kidney function decline. Then, probably 100 was where we saw the strongest association and that's what people should take home clinically. If somebody has an albuminuria greater than 100, these are people that are high risk of having more kidney damage and need to be aggressively monitored, and probably referred to a nephrologist for the management of that.

LP:  What's the next step for research in this area?

SS:  Identifying rapid eGFR decline and identifying albuminuria as a biomarker of rapid kidney function decline. This helps us develop clinical trials so we could identify patients that are high risk, and then also look at these as outcomes to help avert progressive kidney damage. As eventually, these patients requiring dialysis are dying early from their kidney disease. Right now, our data supports that in albuminuria of greater than 100 should be something that people should be screened for and included in clinical trials. Improving that albuminuria is a reasonable target for interventions.

LP:  Is there anything else that you would like to mention?

SS:  I think that the major part of this study was looking at what's the natural history of kidney function in people with sickle cell disease, and what's the rate of decline. We observed that about a third of patients had a rapid decline using general definitions. In the more rapid decline of -6, we saw in a considerable number of people 10 to 15%, that predicted early mortality.

And in understanding the biology, possibly ameliorating hemolysis and this red cell breakdown may help preserve kidney function and then using albuminuria as a very important clinical tool. Also, maybe a research outcome to help preserve kidney function.

LP:  Great. Thank you so much for taking the time to join me today.

SS:  Thank you very much for the opportunity to explain our research from the ASH meeting in 2021.