Low-Carbohydrate Diet Score and All-Cause Mortality in Patients With CKD

Obesity and being overweight is the fifth leading cause of mortality worldwide, resulting in the growing popularity and mainstream use of low-carbohydrate diets (LCDs) as a way to lose weight. While previous studies have demonstrated the effectiveness of LODs to produce short-term weight loss and improvements in several risk factors for cardiovascular disease, such as insulin resistance and cholesterol levels, the long-term safety of adhering to a LCD remains controversial.

Most of the previous studies of the safety and long-term effectiveness of LCDs were conducted in the general population and focused on the effects of the dietary components rather than the health conditions of individuals who adhere to a LCD. Diets lower in carbohydrates and higher in protein and fat than more balanced diets may pose the risk of nephrotoxicity, in addition to concerns that saturated fats are risk factors for atherosclerosis, creating the possibility that LCDs pose particular problems for individuals with chronic kidney disease (CKD).

Nanhui Zhang, MD, and colleagues conducted a study designed to examine the association of LCD with all-cause mortality among individuals with and without CKD. Results of the study were reported in the Journal of Renal Nutrition [2022;32(3):301-311].

The study utilized data from the Third National Health and Nutrition Examination Survey (NHANES III), a nationally representative sample of the noninstutionalized US population conducted between 1988 and 1994 by the National Center for Health Statistics of the Centers for Disease Control and Prevention. The study cohort included nonpregnant adults >20 years of age who had (1) complete data on total nutritional intake obtained from dietary interview (n=15,358); (2) complete data on serum creatinine, urine creatinine, and albumin (n=14,388); (3) CKD, defined as an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 or urinary albumin-to-creatinine ratio ≥30 mg/g (n=2072); and (4) total caloric intake per day between 800 and 4200 kcal per day for men and between 500 and 3500 kcal per day for women (n=1954).

Patients with a history of diabetes, cardiovascular disease, or cancer were excluded (n=703). For the group without CKD participants with an eGFR >60 mL/min/1.73 m2 and albumin-to-creatinine ratio ≤200 mg/gm, with all other inclusion criteria remaining, were included. The primary outcome of interest was all-cause mortality. The final cohort included 1158 participants with CKD and 9523 participants without CKD.

The LCD score was calculated based on a 24-hour dietary recall interview. The score ranged from 0 (lowest fat and protein intake and  highest carbohydrate intake) to 30 (highest protein and fat intake and the lowest carbohydrate intake). Mortality was from baseline until December 31, 2015. Multivariable-adjusted hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards regression models. For analyses of all-cause mortality, participants were divided into four categories (quarters) for each of the LCD score, with the lowest quarter always used as a reference.

In the group with CKD, mean daily carbohydrate intake ranged from 61.9% of total energy intake in the first quarter LCD score to 37.9% of total energy intake in the fourth quarter. Compared with participants in the lowest quarter of LCD score, those who had a higher LCD score were more likely to smoke, had a higher body mass index (BMI), a lower intake of dietary fiber, and a higher intake of sodium.

Among the group without CKD, mean daily carbohydrate intake ranged from 61.4% of total energy intake in the first quarter LCD score to 37.6% of total energy intake in the fourth quarter. Those with a higher LCD score had a higher BMI, and a higher intake of sodium and potassium.

Median follow-up was 24 years. During follow-up, there were 751 (65%) documented all-cause deaths in the CKD group and 2624 (28%) all-cause deaths in the non-CKD group. Following adjustment for all potential confounders, there were significant positive associations between the LCD score and all-cause mortality in participants with CKD. Participants in the fourth quarter LCD score group had a higher risk for all-cause mortality compared with those in the first quarter of the LCD score (hazard ratio [HR], 1.51; 95% CI, 1.01-2.25; P for trend=.045). There was no association between the LCD score and all-cause mortality in the group without CKD, following adjustment for all potential confounders.

In analyses of the association between each macronutrient and all-cause mortality in the group with CKD, compared with the highest total carbohydrate intake, those with the lowest total carbohydrate intake had a significantly higher risk of all-cause mortality (HR, 1.56; 95% CI, 1.11-2.19; P for trend=.006). There was a negative association between intake of vegetable protein and the risk of all-cause mortality (HR, 0.61; 95% CI, 0.44-0.84; P for trend=.003). Intake of saturated fatty acids was associated with an increased risk of all-cause mortality for the comparison of the highest quarter with the lowest quarter (HR, 1.53; 95% CI, 1.17-1.99; P for trend=.034).

Limitations to the study cited by the authors included the self-reported design of the study exposure and most of the covariates, the lack of longitudinal data on participants’ dietary intake during the follow-up period, the use of data from NHANES III (1988-1944) rather than more contemporary data, and the lack of data on the progression of CKD.

In conclusion, the researchers said, “The LCD scores were found significantly positively associated with all-cause mortality in adults with CKD, but not in adults without CKD.”

Takeaway Points

  1. Researchers reported results of a study examining the association of a low carbohydrate diet with mortality in a cohort of individuals with and without chronic kidney disease (CKD).
  2. In participants with CKD, there was an association between higher LCD scores (indicating highest protein and fat intake and lowest carbohydrate intake) and all-cause mortality.
  3. There was no association between higher LCD scores and all-cause mortality among participants without CKD.