Worldwide, the leading cause of chronic kidney disease and kidney failure is type 2 diabetes. Only modest benefits are seen with current recommended treatment options for CKD in patients with type 2 diabetes. There is a strong link between obesity and type 2 diabetes, suggesting that intentional weight loss should be explored as an additional treatment option for CKD in that patient population.
There are few data available on whether remission of diabetes mitigates CKD in patients with type 2 diabetes. Because bariatric surgery has been shown to induce remission in a substantial proportion of patients, it provides a model in which to evaluate this concept. The bariatric surgery model also allows researchers to examine whether remission of diabetes is influenced by the presence of CKD. There is a link between kidney disease and insulin resistance, but it is not known whether patients with type 2 diabetes are less likely to achieve remission following bariatric surgery due to underlying insulin resistance or other factors related to CKD.
Allon N. Friedman, MD, and colleagues conducted a study designed to examine whether remission of diabetes following bariatric surgery influences estimated glomerular filtration rate (eGFR), proteinuria, and prognostic risk for CKD. The researchers also sought to determine if the presence of baseline CKD influences the likelihood of diabetes remission following bariatric surgery. Results of the study were reported in the American Journal of Kidney Diseases [2019;74(6):761-770].
The study included a large prospective multicenter cohort of patients with obesity and type 2 diabetes who underwent bariatric surgery and had regular follow-up over 5 years ; the participants were part of the LABS-2 (Longitudinal Assessment of Bariatric Surgery-2) study.
Of the 737 study participants, 71% were women, 85% were white, and 75% had some postsecondary school education. Median hemoglobin A1c level was 6.9%. More than 78% of the cohort used two or more noninsulin diabetes medications, and 28% required insulin. Median eGFR was 94 mL/min/1.73 m2; 12% of participants had eGFR <60 mL/min/1.73 m2. Median urinary albumin-creatinine ratio (UACR) was 8.9 mg/g; 22% of participants had moderately/severely increased albuminuria. As a measure of prognosis, 18.8%, 8%, and 3.3% of participants were in the moderately increased, high, and very high Kidney Disease Improving Global Outcomes CKD risk categories, respectively
By the end of year 5, median percent weight loss was 24%, change in eGFR was negligible, 34% had regression of their moderately/severely increased albuminuria, and 47% achieved remission of diabetes.
The researchers examined the relationship between post-bariatric surgery diabetes remission and eGFR and UACR during follow-up in separate adjusted analyses. There was no significant association between remission of diabetes and eGFR after surgery; this observation remained true even following exclusion of patients with hyperfiltration. There were associations between higher eGFR after surgery and shorter time elapsed since surgery, younger age at the time of surgery, higher household income, lower baseline systolic blood pressure, higher baseline eGFR, and Roux-en-Y gastric bypass (vs laparoscopic adjustable gastric banding) as surgery type.
Compared with patients with no remission of diabetes, those with partial or complete remission had lower odds of moderately/severely increased albuminuria following surgery (risk ratio [RR], 0.66; 95% confidence interval [CI], 0.48-0.90) following adjustment for baseline characteristics. In sensitivity analysis that excluded three patients with baseline UACRs >2000 mg/g, results were similar (RR, 0.70; 95% CI, 0.50-0.97). There were also significant associations between lower odds of moderately/severely increased albuminuria and younger age at time of surgery, female sex, white race, lower baseline UACR and insulin sensitivity by homeostatic model assessment, and no use of renin-angiotensin-aldosterone-blocking agents.
There was a significant association between complete or partial remission of diabetes at 5 years and greater likelihood of stabilization in the prognostic risk for CKD, compared with no remission. The association was dependent on baseline ghrelin levels (P=.02 for interaction between baseline ghrelin level and diabetes remission). Other baseline characteristics associated with stabilization of prognostic risk were private medical insurance, lower baseline systolic blood pressure, no use of renin-angiotensin-aldosterone-blocking agents, and being in a moderately increased or high versus low CKD risk category.
There was an association between increased odds of partial or complete diabetes remission and higher baseline eGFR (P<.001); this effect was amplified at higher C-peptide levels. Conversely, there was no association between baseline UACR and diabetes remission (odds ratio, 1.004; 95% CI, 0.999-1.01).
Limitations to the findings cited by the authors included lack of a sufficient number of patients with established or advanced kidney disease or long enough follow-up to assess outcomes such as death or kidney failure; lack of a comparison group, preventing the researchers from determining the relative effects of bariatric surgery; not including episodes of hospitalizations and acute kidney injury in the analyses; and lack of kidney biopsies to determine the precise cause of kidney disease in the study participants.
“In summary, we report that partial or complete remission of type 2 diabetes at 5 years after bariatric surgery is associated with improvement in moderately/severely increased albuminuria and stabilization of prognostic risk for CKD. Additionally, worse kidney function or risk at time of bariatric surgery was linked to a lower likelihood of diabetes remission. Finally, ghrelin was associated with salutary effects on prognostic risk for CKD. These intriguing findings warrant further study to determine whether and through what mechanisms bariatric surgery can prevent or delay the progression to kidney failure in this population and identify which patients would most benefit,” the researchers said.
Takeaway Points
- Researchers conducted a prospective observational study to assess whether remission of diabetes after bariatric surgery influences estimated glomerular filtration rate (eGFR), proteinuria, and prognostic risk for chronic kidney disease (CKD) in patients with type 2 diabetes.
- There was no independent association between diabetes remission at 5 years post-surgery and eGFR; there was an association with lower risk for moderate/severe increase in albuminuria.
- There was also an association between diabetes remission and stabilization in prognostic risk for CKD.
