New Guidelines Address Diabetes Management in Kidney Disease

Miriam E. Tucker

November 09, 2020

A new guideline from the Kidney Disease: Improving Global Outcomes (KDIGO) group addressing issues around diabetes management in patients with chronic kidney disease (CKD) has just been published in synopsis form in Annals of Internal Medicine.

The full guideline, including 12 recommendations and 48 practice points for clinicians caring for patients with diabetes and CKD, was published last month in Kidney International and on the KDIGO website.

More than 40% of people with diabetes develop CKD, and a significant number develop kidney failure requiring dialysis or transplant. This is the first guidance from KDIGO to address the comorbidity.  

The new synopsis is aimed at primary care and non-nephrology specialist clinicians who manage patients with diabetes and CKD, in addition to nephrologists, first author Sankar D. Navaneethan, MD, told Medscape Medical News.

"Most of these patients are in the hands of primary care, endocrinology, and cardiology. We want to emphasize when they see patients with different severities of kidney disease [is] what are some of the things they have to be cognizant of," said Navaneethan, professor of medicine and director of clinical research in the section of nephrology at Baylor College of Medicine, Houston, Texas.

The synopsis summarizes key recommendations from the larger guidance regarding comprehensive care needs, glycemic monitoring and targets, lifestyle interventions, glucose-lowering therapies, and educational/integrated care approaches.

It does not depart from prior diabetes guidelines, but it does provide advice for specific situations relevant to CKD, such as the limitations of A1c when estimated glomerular filtration rate (eGFR) drops below 30 mL/min/1.73m2, and dietary protein consumption. It is based on published evidence up until February 2020.

For the nephrologist audience in particular, Navaneethan said, "we wanted to highlight team-based care, interacting with other specialists and working with them."

"We [nephrologists] are more used to team-based care in dialysis patients...So we wanted to highlight that self-management programs and team-based care are important for empowering patients."

"As nephrologists, we might not be comfortable starting patients on an SGLT-2 [sodium-glucose cotransporter-2] inhibitor. We may need to reach out to our endocrinology or primary care colleagues and learn from them," he explained.

RAS Inhibitor Use, Smoking Cessation, Glycemic Targets

Under "comprehensive care," the guideline panel recommends treatment with an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker — renin-angiotensin system (RAS) blockade — for patients with diabetes, hypertension, and albuminuria (albumin-creatinine ratio > 30 mg/g).

These medications should be titrated to the highest approved tolerated dose, with close monitoring of serum potassium and serum creatinine levels within 2-4 weeks of initiation or change in dose.

The document guides clinicians on that monitoring, as well as on RAS blockade use in patient subgroups, use of alternative agents, and mitigation of adverse effects.

Patients with diabetes and CKD who use tobacco should be advised to quit.

The group recommends A1c to monitor glycemic control in patients with diabetes and CKD not receiving dialysis.

However, when eGFR is below 30 mL/min/1.73m2, A1c levels tend to be lower due to shortened erythrocyte lifespan, which interpretation should take into account. Continuous glucose monitoring (CGM) can be used as an alternative because it is not affected by CKD.

Glycemic targets should be individualized depending on hypoglycemia risk, ranging from < 6.5% to < 8.0% for A1c or time in range of 70-180 mg/dL for CGM readings.

SGLT2 Inhibitors, Metformin, and GLP-1 Agonists

The panel also recommends treatment with both metformin and an SGLT2 inhibitor for patients with type 2 diabetes, CKD, and an eGFR ≥ 30 mL/min/1.73m2.

For those who do not achieve glycemic targets or who cannot take those medications, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist can be used instead.

Clinical trial data are summarized for the SGLT2 inhibitor canagliflozin supporting its use in patients with CKD specifically, along with mitigation of adverse events. Last year, the US Food and Drug Administration approved this agent to slow the progression of diabetic nephropathy based on the CREDENCE study.

Results from the DAPA-CKD trial showing CKD reduction with another SGLT2 inhibitor, dapagliflozin, were not available at the time the new document was written, nor was the recent study showing diabetic CKD benefit for the novel mineralocorticoid receptor antagonist finerenone, Navaneethan noted.      

The panel determined that there is insufficient evidence for adding other glucose-lowering agents to insulin in patients with type 1 diabetes and CKD.

Lifestyle Interventions: Dietary Protein, Sodium, and Physical Activity

Most of the dietary guidance for patients with diabetes and CKD is the same as for the general population, including a recommendation to eat a diet high in vegetables, fruits, whole grains, fiber, legumes, plant-based proteins, unsaturated fats, and nuts, and lower in processed meats, refined carbohydrates, and sweetened beverages.

However, the guideline details two key areas that differ, one with regard to protein intake and the other on sodium.

Although lower protein intake had been advised in the past for patients with CKD, clinical trial evidence has not shown protein restriction to reduce glomerular hyperfiltration or slow kidney disease progression.

Therefore, the same level recommended for the general population — 0.8 g/kg/day — is also advised for those with diabetes and CKD who are not on dialysis.

Those who are on dialysis can increase daily protein intake to 1.0-1.2 g/kg/day to offset catabolism and negative nitrogen imbalance.

Because kidney function decline is associated with sodium retention that can raise cardiovascular risk, sodium should be limited to less than 2 g/day (or less than 90 mmol or 5 g of sodium chloride per day).

The panel also recommends moderate-intensity physical activity for at least 150 minutes per week or to tolerance.

"We wanted to emphasize how important lifestyle is. It's the foundation you want to build on. You can take medications without all these other things — exercise, diet, weight loss — but they won't be nearly as effective," Navaneethan commented.

Self-Management Education, Team-Based Care

The final section of the synopsis advises that people with diabetes and CKD receive structured self-management educational programs, and that "policymakers and institutional decision-makers implement team-based, integrated care focused on risk evaluation and patient empowerment to provide comprehensive care in patients with diabetes and CKD."

Despite limited data for those measures specifically in patients with diabetes and CKD, "the working group believed that well-informed patients would choose self-management as the cornerstone of any chronic care model; therefore, a high value was placed on the potential benefits of self-management education programs in persons with diabetes and CKD."

And regarding team-based care, "Despite a paucity of direct evidence, the working group judged that multidisciplinary integrated care for patients with diabetes and CKD would represent a good investment."

The guidelines will likely be updated in the next 1 to 2 years, Navaneethan told Medscape Medical News.

Navaneethan has reported receiving consultancy fees from Bayer, Boehringer Ingelheim, Reata, and Tricida and research support from Keryx.

Ann Intern Med. Published online November 9, 2020. Abstract

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