CKD is associated with increased morbidity and mortality in patients with diabetes. The incidence of ESRD secondary to diabetes was estimated to be 47% in 2017. Adequate evaluation of blood glucose is key to optimizing glycemic control and preventing the development of hypoglycemia. However, blood glucose assessment is fraught with difficulties in this population. A recent review explored the use of CGM in the management of patients with diabetes and CKD/ESRD.

Measures of glycemic control such as glycosylated hemoglobin A1c (HbA1c), fructosamine, or glycated albumin are less reliable in diabetic patients with CKD and ESRD. Factors that affect erythropoiesis or the lifespan of the red blood cell will affect Hb1Ac. Iron or vitamin B12 deficiency increase HbA1c, while the use of iron therapy or erythropoietin reduce HbA1c. The presence of uremia may also interfere with the interpretation of HbA1c.

Glycated albumin only reflects glycemic control for the last 2 to 3 weeks, whereas Hb1Ac reflects glycemic control for the last 2 to 3 months. Further, glycated albumin is affected by low albumin states or by increased protein turnover, which can occur with chronic inflammation. Uremia and reduced renal clearance can also adversely impact the interpretation of glycated albumin concentrations. As with glycated albumin, fructosamine is affected by abnormalities in albumin metabolism, increased protein loss in CKD, and uremia, although it may be more stable than other monitoring tools.

CGM offers the potential of bypassing the above limitations of standard measures of blood glucose monitoring. It can provide a more comprehensive and reliable assessment of glycemic control. With CGM, there is a dynamic equilibrium due to concentration gradients between interstitial and blood glucose. Interstitial glucose is absorbed into the filament of the CGM device, and an electrochemical reaction with the sensor determines the concentration of interstitial glucose.

Sensors in the CGM use enzymatic electrochemical reactions to determine interstitial glucose levels. However, glucose oxidase-peroxidase sensors are subject to interferences by both endogenous and exogenous substances, including hypoxia, uric acid, uremia, hematocrit, a pH less than 6.95, ascorbic acid, acetaminophen, xylose, and ethanol. Glucose dehydrogenase–based detectors using pyrroloquinoline quinone result in falsely elevated blood glucoses if icodextrin dialysate is utilized.

HbA1c readings are still reliable in CKD stages G1-G3b; however, the correlation between HbA1c and main senor glucose values decreases when CKD reaches stages G4-5. This is in part due to the use of iron supplements and erythropoietin. CGM is useful for this latter group of CKD patients, including those undergoing dialysis or receiving a kidney transplant, and has been endorsed by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines as an alternative glycemic index.

Clinical targets for glycemic management with CGM include a time in range goal of >70% with a glucose level >3.9 mmol/L (70 mg/dL) but <10 mmol/L (180 mg/dL) in patients with diabetes without complications; <25% time above range reflecting significant hyperglycemia (i.e., blood glucose >10 mmol/L or 180 mg/dL); and <5% time below range of <3.9 mmol/L (70 mg/dL) indicating hypoglycemia. The impact of these targets in reducing complications and death remain to be determined.

An advantage of CGM over other forms of glucose monitoring is that it provides a comprehensive 24-hour profile that can be used to assess the relationships between glycemic variation, timing of dialysis regimens, and insulin administration. This is especially important since the dialysate and dialysis membrane can contribute to glucose variability. This leads to "glycemic disarray" in which the blood glucose drops during hemodialysis (HD) and then rebounds during the postdialysis period, resulting in hyperglycemia. Glycemic shifts take place with diffusion of plasma glucose into erythrocytes and loss in the dialysate. This generally results in a loss of about 15 to 30 grams of glucose during HD.

Although hyperglycemia can occur when there is a lack of counter-regulatory effects, patients may present with hypoglycemia and asymptomatic hypoglycemia. Asymptomatic hypoglycemia is only captured with the use of CGM. These pre- and post-HD glucose excursions increase glucose variability, oxidative stress, and inflammation, which can lead to poor outcome. CGM can allow prompting of interventions of these glucose variations.

Numerous factors affect glycemic control in patients undergoing peritoneal dialysis (PD). These include the rate of peritoneal absorption of glucose, which is affected by the glucose concentration in the dialysate (e.g., icodextrin leads to sustained ultrafiltration), dwell time, and status of membrane transport; diffusing capacity of the peritoneal membrane; and the timing, route, and dose of insulin. As in HD, the glycemic profile of patients on PD can be comprehensively assessed using CGM, allowing for optimization of the drug regimen.

While there are limitations to the use of CGM in dialysis patients, such as potential sensor interferences, false-positive hypoglycemic alerts, reduced accuracy in lower hypoglycemic ranges or during rapid blood glucose changes, the use of real-time CGM or the interaction of CGM with fully automatic, closed-loop insulin delivery systems can allow for more precise glycemic control.

Pharmacists should be aware of the benefits and limitations of CGM in the management of diabetes in patients with CKD and ESRD so that they can optimally use technology to enhance patients' drug regimens.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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