Spotlight on diabetes and chronic kidney disease

A study showed that chronic kidney disease has declined among U.S. adults with diabetes. A meta-analysis found that sodium-glucose cotransporter-2 inhibitors prevented kidney decline similarly in those with and without diabetes. A survey identified knowledge gaps among prescribers on this topic.

Several recent studies looked at patients with diabetes and chronic kidney disease (CKD).

First, a letter published by the New England Journal of Medicine on Oct. 13 estimated the incidence of CKD among adults with diabetes in 2015 to 2020 using databases of two U.S. health care systems. Overall, the study found that the incidence of CKD among those with diabetes declined from 81.6 cases per 1,000 person-years (95% CI, 78.0 to 85.2) in 2015 and 2016 to 64.0 cases per 1,000 person-years (95% CI, 62.2 to 65.9) in 2019 and 2020. Trends were similar across subgroups by age, race, and ethnicity, but some ethnic groups had higher incidence than others; compared to White patients, the hazard ratio for CKD was 1.56 (95% CI, 1.38 to 1.77) for Native Hawaiian or other Pacific Islander patients, 1.41 (95% CI, 1.33 to 1.50) for Black patients, 1.33 (95% CI, 1.19 to 1.50) for American Indian or Alaska Native patients, and 1.25 (95% CI, 1.20 to 1.30) for Hispanic or Latinx patients. “Despite a recent decline, the persistently high incidence of CKD in the United States is troubling, given the large increase in the prevalence of diabetes and its accompanying high rates of kidney failure,” said the authors, who noted that less than 10% of U.S. patients with early-stage CKD are aware of their condition.

A meta-analysis, published by The Lancet on Nov. 6, looked at the impact of diabetes on the effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on kidney outcomes. Researchers included participants from 13 trials, 74,804 (82.7%) with diabetes (>99% type 2) and 15,605 (17.3%) without. Compared with placebo, SGLT-2 inhibitors significantly reduced the risk of CKD progression (relative risk, 0.63; 95% CI, 0.58 to 0.69). The risk reduction was similar in patients with and without diabetes. Four of the trials included only patients with CKD and found similar benefits with SGLT-2 inhibitors regardless of the cause of CKD. Similar risk reductions were also seen with varying kidney function at baseline. “In all the trial populations studied to date, the absolute benefits of SGLT2 inhibition considerably outweighed any serious hazards,” and these findings “support a central role for SGLT2 inhibitors as a disease-modifying therapy for chronic kidney disease, irrespective of diabetes status, primary kidney diagnosis, or level of kidney function,” said the authors. They estimated that for every 1,000 patients with CKD treated for a year with an SGLT-2 inhibitor, 11 first kidney disease progression events would be prevented in patients with diabetes and 15 would be prevented in those without diabetes. An accompanying editorial praised the analysis, saying that it can be “expected to change chronic kidney disease guidelines with its robust findings on the benefits of SGLT2 inhibition in a wide range of patients with chronic kidney disease, including many without diabetes, although outstanding questions remain.” The editorial continued, “Nephrologists should now work with and empower primary health-care providers to ensure that SGLT2 inhibitors are implemented as a foundational therapy for chronic kidney disease, with early initiation in individuals at risk of chronic kidney disease progression to minimize the risk of kidney failure and its associated cardiovascular complications.”

Finally, a small study published by the Journal of General Internal Medicine on Oct. 31 assessed prescribers' knowledge about use of diabetes drugs in patients with type 2 diabetes and CKD. Researchers surveyed 74 primary care clinicians and 31 endocrinologists and conducted more extensive interviews with two endocrinologists, six general internists, and one nurse practitioner. They generally found that metformin was the clinicians' most common choice for patients with diabetes and CKD but that endocrinologists were more knowledgeable about guidance regarding appropriate use of metformin in patients with reduced kidney function. In response to vignettes, both endocrinologists and primary care clinicians relatively rarely chose SGLT-2 inhibitors or glucagon-like peptide-1 receptor agonists for these patients. The study authors concluded that clinicians have substantial uncertainty about how to treat patients with diabetes and CKD. “This suggests opportunities to improve care. In particular, the data suggest potential underuse of metformin in stage 3 CKD and overuse in stage 4; underuse of [glucagon-like peptide-1 receptor agonists] and [SGLT-2 inhibitors]; and perhaps overuse of insulin and sulfonylurea in patients with advanced CKD,” said the authors. They called for clinician education and increased access to specialists and electronic decision support.