‘It’s never too late’: Tailoring glucose management in advanced CKD
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Glucose management remains important for adults with diabetes and advanced chronic kidney disease as a strategy to prevent or delay progression to dialysis, prevent cardiovascular events and improve quality of life, according to a speaker.
“Why treat advanced CKD with glucose lowering? Isn’t it too late to achieve anything? I have this discussion with my nephrology colleagues quite often,” Vivian A. Fonseca, MD, professor of medicine at Tulane University in New Orleans said during an online presentation at the virtual Heart in Diabetes conference. “My answer is, if you have someone with an [estimated glomerular filtration rate] of 30 mL/min/1.73 m2, you want to delay their progression to dialysis and transplant as long as you can. That is a very big challenge to the quality of life those patients will experience.”
More important still is progression to other microvascular complications of diabetes, including blindness and amputation, Fonseca said. CV events, such as congestive heart failure, are also common among patients with advanced CKD. Additionally, the cost of end-stage renal disease remains the most expensive complication of diabetes, he said.
“This is a very serious matter,” Fonseca said. “Kidney diseases is a frequent complication of type 1 and type 2 diabetes ... once patients with diabetes have kidney disease, their CV risk is greatly amplified. Many patients with CKD actually die from CVD before they reach needing dialysis.”
Assessing risk
Even with the advance of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) therapy in CKD treatment, residual risk remains much in the same way there is residual risk after lipid-lowering therapy in CVD management, Fonseca said. Tailored treatment strategies that avoid causing hypoglycemia are key in advanced CKD management, taking into consideration CKD stage, Fonseca said. An additional challenge in this population is how to properly assess risk; HbA1c is not as reliable a measurement among those with diabetes and advanced CKD, Fonseca said. He recommended fructosamine measurements, adding that glycated albumin measurements were recently approved and should be available soon.
“We also have continuous glucose monitoring for these patients,” Fonseca said. “Fructosamine reflects serum proteins that bind to fructose and reflect glycemia over 2 to 3 weeks. The problem is it fluctuates a lot, and that might reflect acute changes in protein concentrations. Glycated albumin may be a bit more reliable, but has not been studied in people with advanced CKD.”
CGM data clearly show that glycemic managemet differs depending on dialysis status, and any treatment should reflect that, Fonseca said.
Slowing progression, improving outcomes
Many changes in treatment are needed in advanced CKD, and management can be challenging, Fonseca said. Insulin is commonly used in CKD due to contraindications for oral diabetes agents; Fonseca said insulin doses should be reduced in advanced CKD due to decreased clearance and food intake and higher risk for hypoglycemia.
“In the past, the go-to treatment for people with diabetes and CKD has been insulin,” Fonseca said. “It is very challenging, and I do not think we should consider it as the go-to treatment.”
In the setting of an eGFR of 30 mL/min/1.73 m2 or lower, metformin is contraindicated due to risk for lactic acidosis. Sulfonylurea therapy has been used, but prolonged hypoglycemia remains a concern in these patients, who can sometimes be malnourished, he said.
Long-acting GLP-1 receptor agonists have been shown to reduce CV risk and are relatively safe, he said. SGLT2 inhibitors have demonstrated nephroprotective benefits in addition to reducing risk for hospitalization for heart failure and other CV risk factors. In September 2019, the FDA approved a new indication for the SGLT2 inhibitor canagliflozin (Invokana, Janssen) to reduce the risk for end-stage renal disease, worsening of kidney function, CV death and hospitalization for heart failure among adults with type 2 diabetes and diabetic kidney disease, based on results from the phase 3 CREDENCE study, which was stopped early due to overwhelming benefit. Similar data are anticipated with the SGLT2 inhibitor dapagliflozin (Farxiga), but a study is ongoing.
Fonseca cautioned that many participants in the early SGLT2 inhibitor trials were low-risk patients with eGFRs that did not fall below 45 mL/min/1.73 m2.
“We don’t really have much data on the group that I was asked to talk about, which is an eGFR below 30 mL/min/1.73 m2,” Fonseca said. “But some of these patients in CREDENCE dropped their eGFR, and some managed to enter with an eGFR less than 30 mL/min/1.73 m2, but the numbers are very small. It is a question of numbers. There seems to be benefit, but we need more data.”
Data also show promise for the investigational drug finerenone, Fonseca said. As Healio reported in July, topline findings from the FIDELIO-DKD study showed finerenone delayed the progression of CKD and reduced risk for CV events among adults with type 2 diabetes compared with placebo; full data will be presented at an upcoming meeting.
Additional blood pressure reduction in this setting is also important, but challenging, Fonseca said.
“I want to point out that these drugs all lower BP, and management and guidelines on CKD and BP have changed a lot, and that is still part of management in diabetes,” Fonseca said. “We still use ACE inhibitors and ARBs as much as possible, without stopping them if you can help it. The figures for systolic BP keep changing but aim for less than 130 mm Hg in all CKD patients.”
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Fonseca VA. Managing hyperglycemia in T2DM with class 4-5 CKD. Presented at: Heart in Diabetes CME Conference; Aug. 21- 24, 2020, 2019; (virtual meeting).
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