Renal function following three distinct weight loss dietary strategies during 2 years of a randomized controlled trial

Abstract

Objective: This study addressed the long-term effect of various diets, particularly low-carbohydrate high-protein, on renal function on participants with or without type 2 diabetes.

Research design and methods: In the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT), 318 participants (age, 51 years; 86% men; BMI, 31 kg/m(2); mean estimated glomerular filtration rate [eGFR], 70.5 mL/min/1.73 m(2); mean urine microalbumin-to-creatinine ratio, 12:12) with serum creatinine <176 μmol/L (eGFR ≥ 30 mL/min/1.73 m(2)) were randomized to low-fat, Mediterranean, or low-carbohydrate diets. The 2-year compliance was 85%, and the proportion of protein intake significantly increased to 22% of energy only in the low-carbohydrate diet (P < 0.05 vs. low-fat and Mediterranean). We examined changes in urinary microalbumin and eGFR, estimated by Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration formulas.

Results: Significant (P < 0.05 within groups) improvements in eGFR were achieved in low-carbohydrate (+5.3% [95% CI 2.1-8.5]), Mediterranean (+5.2% [3.0-7.4]), and low-fat diets (+4.0% [0.9-7.1]) with similar magnitude (P > 0.05) across diet groups. The increased eGFR was at least as prominent in participants with (+6.7%) or without (+4.5%) type 2 diabetes or those with lower baseline renal function of eGFR <60 mL/min/1.73 m(2) (+7.1%) versus eGFR ≥ 60 mL/min/1.73 m(2) (+3.7%). In a multivariable model adjusted for age, sex, diet group, type 2 diabetes, use of ACE inhibitors, 2-year weight loss, and change in protein intake (confounders and univariate predictors), only a decrease in fasting insulin (β = -0.211; P = 0.004) and systolic blood pressure (β = -0.25; P < 0.001) were independently associated with increased eGFR. The urine microalbumin-to-creatinine ratio improved similarly across the diets, particularly among participants with baseline sex-adjusted microalbuminuria, with a mean change of -24.8 (P < 0.05).

Conclusions: A low-carbohydrate diet is as safe as Mediterranean or low-fat diets in preserving/improving renal function among moderately obese participants with or without type 2 diabetes, with baseline serum creatinine <176 μmol/L. Potential improvement is likely to be mediated by weight loss-induced improvements in insulin sensitivity and blood pressure.

Trial registration: ClinicalTrials.gov NCT00160108.

Figure 1

A: Two-year changes of eGFR within baseline stages for CKD stage III (black line, eGFR ≤60 mL/min/1.73 m², moderate to severe) and CKD stages I/II (dashed line, eGFR >60 mL/min/1.73 m²; mild to normal). *P < 0.05 for improvement within groups after 2 years of intervention. B: Two-year changes in eGFR across dietary intervention groups receiving low-fat diet (black line), Mediterranean diet (gray line) and low-carbohydrate diet (dashed line). *P < 0.05 for improvement within groups after 2 years of intervention. Two-year changes of eGFR across dietary intervention groups and CKD stage for eGFR >60 mL/min/1.73 m² (CKD stage I/II) (C), and eGFR <60 mL/min/1.73 m² (CKD stage III) (D) for patients receiving a low-fat diet (black line), Mediterranean diet (gray line), and a low-carbohydrate diet (dashed line). *P < 0.05 for improvement within groups after 2 years of ntervention. E: Two-year changes of eGFR across diabetes status for those with (black line) and without (dashed line) type 2 diabetes. *P < 0.05 for improvement within groups after 2 years of intervention.

Figure 2

Two-year changes in albumin-to-creatinine ratio across microalbuminuria at baseline. The urine albumin-to-creatinine ratio was ≥17 for men and ≥25 for women. (No microalbuminuria, n = 299; microalbuminuria, n = 23). ■ = baseline, □ = after 2 years of intervention. *P < 0.05 for improvement within groups after 2 years of intervention. †P < 0.05 for improvement between groups after 2 years of intervention.