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Diabetes and Chronic Kidney Disease

Posted on March 17, 2019

Older adults with diabetes and chronic kidney disease (CKD) are at an increased risk of cognitive impairment and dementia, frailty, dysglycemia, and polypharmacy.

A recent review article published on February 15, 2019 discussed the complexity of older adults who live with both diabetes and chronic kidney disease. Risk of dementia is increased with declining kidney function, longer duration of diabetes, hypoglycemia, and HbA1c levels greater than 7% in patients with mild cognitive impairment. In a cross-sectional study of 1,358 older adults with diabetes and chronic kidney disease, compared with individuals who had no diabetes or kidney disease, patients with both conditions had a multi-adjusted odds ratio of 4.23 for cognitive impairment. Mechanisms common to both diabetes and CKD, such as inflammation, peripheral vascular disease, and cardiovascular disease, might explain these findings. During clinical assessments, providers might periodically screen for cognitive dysfunction and depression or involve geriatric teams to help with this screening.

Another complication is sarcopenia and frailty. In early diabetes, poor glycemic control, oxidative stress, and inflammation have been postulated to play a role in the development of sarcopenia, whereas in the later stages of diabetes, complications, including peripheral neuropathy, play more of a role. Insulin resistance, even in patients without diabetes, has also been linked with protein energy wasting and sarcopenia in those with CKD. Vitamin D deficiency is also a risk factor for frailty and is especially apparent in patients with diabetes and CKD. There are multiple frailty measures available, many of which require minimal training for accurate use. Good nutrition with vitamin D and protein intake has been associated with improvements in muscle mass and function. Physical rehabilitation and multi-component exercise programs incorporating balance exercises, gait re-training, and strength, power, and resistance training have the potential to reverse frailty deficits.

Older adults with diabetes and CKD are at risk of both hyperglycemia and hypoglycemia. Even without underlying diabetes, an eGFR< 60 ml/min/1.73m2 has been linked with insulin resistance and reductions in insulin secretion. Reasons for hypoglycemia in older adults with diabetes and CKD could be many. Many anti-hyperglycemic medications are cleared by the kidneys, putting patients with CKD at increased risk of drug-induced hypoglycemia. Muscle wasting and dysfunction might also contribute to reduced insulin clearance. Patients with CKD and diabetes also have more medical comorbidities, which might increase their susceptibility to hypoglycemia. Additionally, they often have longer-standing diabetes, which is a known risk factor for hypoglycemia.

These patients require special diabetes-related monitoring, which includes monitoring of kidney function and glycemic control.

Some of the challenges for monitoring are that using equations such as Cockcroft–Gault to estimate creatinine clearance were not specifically developed in older adults. In addition, there are limitations to using creatinine to estimate glomerular filtration rate (GFR) in older patients. Creatinine production is dependent upon muscle mass, and in older adults, the production of creatinine can be heterogeneous. Patients can also have variable creatinine secretion. Therefore, despite having a normal creatinine, older adults can have “concealed renal failure” with a declining GFR. Where HbA1c is suggested for monitoring glycemic control in most healthy individuals, this test is affected by reduced red cell survival, use of erythropoietin, hemoglobin modifications, and mechanical destruction of blood cells. These conditions are often present in CKD, and the correlation between HbA1c and fasting glucose weakens with lower kidney function. Attention to capillary and venous blood glucose is important in older adults with diabetes and CKD.

Another issue to consider is polypharmacy. Before providers prescribe new medications, the medication lists of older adults with CKD should be reviewed. Where patients are at increased risk of polypharmacy, their need for prescribed therapies might be re-evaluated, and medications should be reconciled. Providers might also look for nephrotoxic medications and use drug interaction checkers when reviewing their medication lists.

Glycemic targets should be based upon the individual patient. Given the heterogeneity of older adults with diabetes, there are no age specific recommendations for glycemic control. Targets should depend upon their function, life expectancy, and risk of hypoglycemia. It is also important to identify overtreatment and to de-intensify and de-prescribe to minimize harm.

Providers could also involve multidisciplinary care teams in the management of older adults with diabetes and CKD. Geriatricians can bring expertise in managing multi-morbidity, de-prescribing, falls risk reduction, and rehabilitation. In older adults, multidisciplinary teams (i.e., geriatricians, diabetes nurse educators, registered dietitians) can improve glycemic management and self-care behaviors when compared with usual diabetes care.

The article concluded to suggest a patient-centered, individualized approach to their best management. Where the number of patients living with these conditions will continue to increase, more efforts might be taken to understand their outcomes and the ideal therapies and targets to use in this population.

Practice Pearls:

Older adults with chronic kidney disease and diabetes can experience many challenges, including cognitive impairment and dementia, frailty, dysglycemia, and polypharmacy.
Providers should pay close attention to their comorbidities and functional status, practice safe and cautious prescribing, individualize their glycemic targets, closely monitor them, involve other care professionals in their management, and provide them with patient-centered care.
More research is required to identify the ideal therapies and targets to use in this population.
References:

Clemens KK, O’Regan N, Rhee JJ. Diabetes Management in Older Adults With Chronic Kidney Disease. Curr Diab Rep. 2019 Feb 15;19(3):11.

Yin Z, Yan Z, Liang Y, Jiang H, Cai C, Song A, et al. Interactive effects of diabetes and impaired kidney function on cognitive performance in old age: a population-based study. BMC Geriatr. 2016;16:7

Dahlia Elimairi, Pharm D Student UC Denver Skaggs School of Pharmacy

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