SUMMARY
Chronic kidney disease (CKD) affects 10-15% of US adults including 30-40% of persons with diabetes
mellitus (DM), is associated with poor outcomes, and often progresses to requiring dialysis or transplantation.
Half of all Americans with CKD also have DM. While traditional and emerging pharmacotherapies are often
used in CKD with diabetes (CKD/DM), the synergistic role of dietary interventions has not been well
examined. Low-carbohydrate low-fat diets are often recommended in DM, whereas low-protein diets (LPDs)
are recommended for non-diabetic CKD with increasing emphasis on plant-based protein sources. Evidence
suggests that high-protein diets with greater animal protein content may lead to glomerular hyperfiltration and
faster decline in renal function in patients with CKD/DM. There remains major controversy regarding the
potential risks vs. benefits of plant-based diets in CKD/DM, for which guidelines remain based on expert
opinion. Given conventional dietary restrictions for the management of DM, there is concern that plant-based
LPDs may lead to protein-energy wasting and hyperkalemia, whereas these diets may indeed be most
beneficial in patients with CKD/DM given their faster rates of CKD progression as compared to non-diabetics.
At present, clinical practice guidelines provide conflicting recommendations regarding the amount (low vs.
high) and source (plant vs. animal) of dietary protein intake (DPI) in CKD/DM. Given that prior dietary trials in
CKD such as the 1994 Modification of Diet in Renal Disease (MDRD) study excluded CKD/DM and did not
examine the optimal proportion of plant vs. animal-based proteins, there is urgent unmet need for a rigorous
dietary intervention study to examine the efficacy and safety of patient-centered plant-based diets in CKD/DM.
In the spirit of PAS 20-160 (Small R01s for Clinical Trials Targeting NIDDK Diseases) we propose a pilot
feasibility randomized controlled trial, conducted in parallel with patients' routine follow-up visits at two CKD
clinics within the University of California Irvine, to test the feasibility and safety of implementing a Plant-
Focused Nutrition in CKD/DM (PLAFOND) diet with a DPI of 0.6-0.8 g/kg/d comprised of >2/3 plant-based
sources, vs. standard-of-care renal diet with <1/3 plant-sources and low-potassium content, administrated by
dietitians, over a 6-month period in 120 patients with CKD/DM stage 3-5. We will determine whether the
PLAFOND diet vs. the standard-of-care renal diet can be adhered to with consistent separation in dietary
protein and plant-based proportions at 3- and 6-months. We will also examine nutritional status, physical
performance, and body composition, as well as glycemic measures using traditional metrics and continuous
glucose monitoring, while other biochemical parameters and patient-reported outcomes including CKD-related
symptoms will also be studied. In addition to providing the requisite feasibility and safety data of patient-
centered dietary regimens needed for the design and conduct of future multi-center trials, our proposed study
will have major immediate impact by reinvigorating the critical role of dietary management of CKD/DM.
