Effects of a Lifestyle Intervention on Kidney Outcomes

Lifestyle interventions have proven effective at aiding weight loss and improving risk factors for chronic kidney disease (CKD), including obesity, diabetes, and hypertension. However, their impact on kidney function (measured as estimated glomerular filtration rate [eGFR]) over time has not been widely reported. 

The Action for Health in Diabetes (Look AHEAD) trial randomized patients with diabetes and either obesity or overweight into two groups: one that received an intensive lifestyle intervention and another that received usual care (diabetes support and education). The trial ended early when it found no significant difference between the two groups in terms of cardiovascular morbidity and mortality. 

Using creatinine-based eGFR, researchers led by Linda-Marie U. Lavenburg, DO, conducted a post hoc analysis of Look AHEAD data to determine whether the lifestyle intervention had any significant effect on kidney function over 10 years. Their results were published in Kidney Medicine.  

Look AHEAD participants were 5145 adults aged 45-75 years who were supervised by a primary care provider and had type 2 diabetes, body mass index (BMI) of ≥25 kg/m², and the ability to complete a maximal exercise test. The kidney-focused post hoc analysis included 4901 of those participants whose data were archived in the National Institute of Diabetes and Digestive and Kidney Diseases data repository. 

Median participant age was 58 (interquartile range: 55-64) years, and there was no significant difference in the number of lifestyle intervention versus usual care participants with normal urine albumin-creatinine ratio (UACR; 84% vs 82%), microalbuminuria (13% vs 14%), or macroalbuminuria (3% vs 3%). Both randomization arms were balanced regarding sex (59% female), race/ethnicity (66% non-Hispanic White, 16% non-Hispanic Black, and 14% Hispanic), mean BMI (36 kg/m2), eGFR (89 mL/min/1.73 m²), and serum creatinine level (0.8 mg/dL). The majority (75%) of participants had an eGFR of >80 mL/min/1.73 m².  

All Look AHEAD participants were instructed to eat a low-fat, reduced calorie diet. Those in the lifestyle intervention group were to increase physical activity to 175 minutes/week, with the goal of decreasing their starting body weight by ≥7%. The intervention was individual or group sessions led by a trained interventionist to help the participants meet dietary and physical activity goals using behavior modification techniques.  

The study authors chose slope of eGFR (mL/min/1.73 m2 per year) as the primary study outcome, hypothesizing that the long-term cumulative effect of reduced glomerular pressure would decrease eGFR slope. Secondary outcomes were mean eGFR and slope and mean UACR (mg/mg), used to evaluate the kidney’s response to physiologic changes over the course of follow-up. Serum creatinine, urine albumin, and urine creatinine were measured at baseline, yearly for the first 5 years, and then every other year. 

The researchers evaluated differences in baseline demographics, clinical characteristics, eGFR, and UACR between randomization arms using a two-sample t test or Wilcoxon-rank sum for continuous covariates and the χ2 test of proportions for categorical covariates. They used linear mixed effects modeling with random slopes and intercepts for distinctive participant identifiers to evaluate the association of the randomization arm with within-individual repeated measures of eGFR and UACR over 10 years. 

Kidney function in both groups decreased over the 10-year study period, although there appeared to be a smaller annual decline in the lifestyle intervention arm. There was no significant difference in the eGFR slope between randomization arms (adjusted difference: +0.070 mL/min/1.73 m² per year; 95% CI, −0.032 to 0.17; P=.18) in adjusted and unadjusted analyses. 

Compared with the usual care arm, the lifestyle intervention group had a slightly higher mean eGFR over 10 years of follow-up by +0.73 (95% CI, −0.068 to 1.53; P=.07) relative to the usual care arm in the unadjusted linear mixed effects model. The adjusted mean difference in eGFR over 10 years was +0.40 mL/min/1.73 m² (95% CI, 0.060-0.740; P=.02). Further examination determined that age was a significant effect modifier on mean eGFR; participants aged ≥65 years in the lifestyle intervention group had a slightly higher mean eGFR (+0.99 mL/min/1.73 m²; 95% CI, 0.16-1.82; P=.02) versus the usual care group. Baseline eGFR did not change the effect of the lifestyle intervention on eGFR slope or mean eGFR. There was no significant difference in UACR slope (adjusted: −0.00098 mg/mg per year; 95% CI, −0.0043 to 0.0023; P=.57) or adjusted mean UACR (−0.0054 mg/mg; 95% CI, −0.013 to 0.0026; P=.19) between randomization arms.  

Limitations of the study include the limited generalizability of trials with lengthy follow-up, which often recruit highly motivated participants. Furthermore, there were no participants with kidney disease or significant albuminuria, which could lead to underestimation of the effects of intensive lifestyle interventions in patients with uncontrolled CKD risk factors. 

In summary, the authors wrote, “In patients with type 2 diabetes and preserved kidney function, intensive lifestyle intervention did not change eGFR slope over 10 years. Among participants with baseline eGFR <80, lifestyle intervention had a slightly higher longitudinal mean eGFR than usual care. Further studies evaluating the effects of intensive lifestyle intervention in people with kidney disease are needed.” 

Source: Kidney Medicine