EFFECT OF LOW VS NORMAL PROTEIN DIET ON RENAL FUNCTION RESERVE IN STAGE 3&4 CHRONIC KIDNEY DISEASE:LARGEST RANDOMIZED TRIAL FROM SOUTHEAST ASIA

Renal functional reserve (RFR)—the difference between peak and baseline glomerular filtration rate (GFR)—reflects the adaptive capacity of the kidney. A decline in RFR precedes measurable loss of GFR and may serve as an early biomarker for progression of chronic kidney disease (CKD). This randomized study compared the effect of a low-protein diet (LPD) versus a normal-protein diet (NPD) on absolute (RFR-abs) and relative (RFR-%) renal reserve and rate of GFR decline over six months in stage 3&4 CKD.

This randomized controlled trial (RCT) was conducted at a tertiary nephrology center in India between August 2024-August 2025. Adults aged >18 years with stage 3 or 4 chronic kidney disease (CKD) were enrolled. The study received Institutional Ethics Committee approval prior to commencement.This single-center, randomized, parallel-group trial included 135 patients aged 18 to 60 years attending the nephrology outpatient clinic. Written informed consent was obtained. Patients with acute illness or unstable renal function within 4 weeks, neurological or psychiatric disorders, malignancy, pregnancy or lactation, prior renal transplantation, chronic steroid use, hypercalcemia, alcohol abuse, or chronic liver disease were excluded. Baseline assessments included clinical evaluation, biochemical tests, and renal function measurement using 24-hour creatinine clearance (CrCl) and two plasma-sample technetium-99m diethylenetriamine pentaacetic acid (⁹⁹ᵐTc-DTPA) clearance before and after a standardized 1 g/kg protein load. These measurements were used to calculate absolute and relative renal functional reserve (RFR-abs and RFR-%).Following baseline evaluation, patients were randomized in a 1:1 ratio using a computer-generated sequence with concealed allocation to one of two dietary interventions: Normal Protein Diet (NPD, 0.8 g protein/kg/day) or Low Protein Diet (LPD, 0.6 g protein/kg/day). Dietary adherence was monitored throughout the six-month study period.This composition complies with clinical trial reporting standards, clarifies your study dates, trial type, randomization method, eligibility criteria, assessment techniques, and intervention arms succinctly and clearly.

Of 135 patients (64 NPD, 71 LPD; mean age 52 ± 10 years; M/F = 84/51), both groups showed a significant GFR increase after protein loading at baseline and at six months (p < 0.001). The magnitude of RFR rise was similar at baseline (p = 0.88) but significantly greater in LPD at six months (p = 0.03). Decline in RFR was smaller in LPD compared with NPD by both methods [RFR-abs (DTPA): p = 0.002; RFR-% (DTPA): p = 0.001; RFR-abs (CrCl): p = 0.046; RFR-% (CrCl): p = 0.021], with no significant difference in eGFR change between groups. Lower baseline GFR, higher proteinuria, and older age independently predicted low RFR.

A low-protein diet (0.6 g/kg/day) preserved both absolute and relative RFR better than a normal-protein diet in CKD stage 3–4 without compromising nutritional status. Decline in RFR preceded measurable fall in GFR, supporting its role as an early biomarker for CKD progression. This trial provides first-of-its-kind randomized evidence from India to guide individualized dietary protein restriction in CKD management.